Neurodegenerative disease - Knowledge (XXG)

551:, vision loss, and shortened lifespan. A loss of vision is common first sign of Batten disease. Loss of vision is typically preceded by cognitive and behavioral changes, seizures, and loss of the ability to walk. It is common for people to establish cardiac arrhythmias and difficulties eating food as the disease progresses. Batten disease diagnosis depends on a conflation of many criteria: clinical signs and symptoms, evaluations of the eye, electroencephalograms (EEG), and brain magnetic resonance imaging (MRI) results. The diagnosis provided by these results are corroborated by genetic and biochemical testing. No effective treatments were available to prevent the disease from being widespread before the past few years. In recent years, more models have been created to expedite the research process for methods to treat Batten disease. 626: 503:) is thought to be the most common known cause of sporadic ALS. Early diagnosis of ALS is harder than with other neurodegenerative diseases as there are no highly effective means of determining its early onset. Currently, there is research being done regarding the diagnosis of ALS through upper motor neuron tests. The Penn Upper Motor Neuron Score (PUMNS) consists of 28 criteria with a score range of 0–32. A higher score indicates a higher level of burden present on the upper motor neurons. The PUMNS has proven quite effective in determining the burden that exists on upper motor neurons in affected patients. 219:. It is the most common neurodegenerative disease. Even with billions of dollars being used to find a treatment for Alzheimer's disease, no effective treatments have been found. Within clinical trials stable and effective AD therapeutic strategies have a 99.5% failure rate. Reasons for this failure rate include inappropriate drug doses, invalid target and participant selection, and inadequate knowledge of pathophysiology of AD. Currently, diagnoses of Alzheimer's is subpar, and better methods need to be utilized for various aspects of clinical diagnoses. Alzheimer's has a 20% misdiagnosis rate. 454:

experience early relapsing and remitting episodes of neuronal deterioration following a period of recovery. Some of these individuals may transition to a more linear progression of the disease, while about 15% of others begin with a progressive course on the onset of multiple sclerosis. The inflammatory response contributes to the loss of the grey matter, and as a result current literature devotes itself to combatting the auto-inflammatory aspect of the disease. While there are several proposed causal links between EBV and the

50: 135:. Neurodegeneration can be found in the brain at many different levels of neuronal circuitry, ranging from molecular to systemic.Because there is no known way to reverse the progressive degeneration of neurons, these diseases are considered to be incurable; however research has shown that the two major contributing factors to neurodegeneration are oxidative stress and inflammation. Biomedical research has revealed many similarities between these diseases at the 437:, caused by an autoimmune attack resulting in the progressive loss of myelin sheath on neuronal axons. The resultant decrease in the speed of signal transduction leads to a loss of functionality that includes both cognitive and motor impairment depending on the location of the lesion. The progression of MS occurs due to episodes of increasing inflammation, which is proposed to be due to the release of antigens such as 6885: 314:, may play a role in this disease mechanism. Impaired axonal transport of alpha-synuclein may also lead to its accumulation in Lewy bodies. Experiments have revealed reduced transport rates of both wild-type and two familial Parkinson's disease-associated mutant alpha-synucleins through axons of cultured neurons. Membrane damage by alpha-synuclein could be another Parkinson's disease mechanism. 171: 329:(MAPT) can also cause hereditary PD or increase PD risk. While PD is the second most common neurodegenerative disorder, problems with diagnoses still persist. Problems with the sense of smell is a widespread symptom of Parkinson's disease (PD), however, some neurologists question its efficacy. This assessment method is a source of controversy among medical professionals. The 6897: 6443: 543:(NCLs) – each caused by a specific gene mutation, of which there are thirteen. Since Batten disease is quite rare, its worldwide prevalence is about 1 in every 100,000 live births. In North America, NCL3 disease (juvenile NCL) typically manifests between the ages of 4 and 7. Batten disease is characterized by motor impairment, 1441:

by Medivation, Inc. In 2009 this drug was in phase III clinical trials for use in Alzheimer's disease, and also phase II clinical trials for use in Huntington's disease. In March 2010, the results of a clinical trial phase III were released; the investigational Alzheimer's disease drug Dimebon failed

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along with enzymes is key for the degradation of many proteins that cause proteopathies including polyQ expansions and alpha-synucleins. Research indicates proteasome enzymes may not be able to correctly cleave these irregular proteins, which could possibly result in a more toxic species. This is the

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A current therapeutic target for the treatment of Alzheimer's disease is the protease β-secretase, which is involved in the amyloidogenic processing pathway that leads to the pathological accumulation of proteins in the brain. When the gene that encodes for amyloid precursor protein (APP) is spliced

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Polyglutamine repeats typically cause dominant pathogenesis. Extra glutamine residues can acquire toxic properties through a variety of ways, including irregular protein folding and degradation pathways, altered subcellular localization, and abnormal interactions with other cellular proteins. PolyQ

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Protein degradation offers therapeutic options both in preventing the synthesis and degradation of irregular proteins. There is also interest in upregulating autophagy to help clear protein aggregates implicated in neurodegeneration. Both of these options involve very complex pathways that we are

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is involved with nutrient recycling of macromolecules under conditions of starvation, certain apoptotic pathways, and if absent, leads to the formation of ubiquinated inclusions. Experiments in mice with neuronally confined macroautophagy-gene knockouts develop intraneuronal aggregates leading to

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accumulation provides the underlying causative link between aging and neurodegenerative disease. About 20–40% of healthy people between 60 and 78 years old experience discernable decrements in cognitive performance in several domains including working, spatial, and episodic memory, and processing

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of disease to test potential therapeutic agents. Model organisms provide an inexpensive and relatively quick means to perform two main functions: target identification and target validation. Together, these help show the value of any specific therapeutic strategies and drugs when attempting to

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is particularly harmful because DNA is the blueprint for protein production and unlike other molecules it cannot simply be replaced by re-synthesis. The vulnerability of post-mitotic neurons to DNA damage (such as oxidative lesions or certain types of DNA strand breaks), coupled with a gradual

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to cross the blood-brain barrier and attack myelin on neuronal axons leading to inflammation. Further release of antigens drives subsequent degeneration causing increased inflammation. Multiple sclerosis presents itself as a spectrum based on the degree of inflammation, a majority of patients

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in any form, mediated by an intracellular program. This process can be activated in neurodegenerative diseases including Parkinson's disease, amytrophic lateral sclerosis, Alzheimer's disease and Huntington's disease. PCD observed in neurodegenerative diseases may be directly pathogenic;

393:. Huntington's disease presents itself later in life even though the proteins that cause the disease works towards manifestation from their early stages in the humans affected by the proteins. Along with being a neurodegenerative disorder, HD has links to problems with neurodevelopment. 937:

Damage to the membranes of organelles by monomeric or oligomeric proteins could also contribute to these diseases. Alpha-synuclein can damage membranes by inducing membrane curvature, and cause extensive tubulation and vesiculation when incubated with artificial phospholipid vesicles.

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both contribute to aging. Many of these diseases are late-onset, meaning there is some factor that changes as a person ages for each disease. One constant factor is that in each disease, neurons gradually lose function as the disease progresses with age. It has been proposed that

283:, rigidity, resting tremor and posture instability. The crude prevalence rate of PD has been reported to range from 15 per 100,000 to 12,500 per 100,000, and the incidence of PD from 15 per 100,000 to 328 per 100,000, with the disease being less common in Asian countries. 1442:

in the pivotal CONNECTION trial of patients with mild-to-moderate disease. With CONCERT, the remaining Pfizer and Medivation Phase III trial for Dimebon (latrepirdine) in Alzheimer's disease failed in 2012, effectively ending the development in this indication.

487:(LMNs). Although initial symptoms may vary, most patients develop skeletal muscle weakness that progresses to involve the entire body. The precise etiology of ALS remains unknown. In 1993, missense mutations in the gene encoding the antioxidant enzyme 1221:

PCD can also occur via non-apoptotic processes, also known as Type III or cytoplasmic cell death. For example, type III PCD might be caused by trophotoxicity, or hyperactivation of trophic factor receptors. Cytotoxins that induce PCD can cause

1213:, which fuses with a lysosome to destroy the contents of the autophagosome. Because many neurodegenerative diseases show unusual protein aggregates, it is hypothesized that defects in autophagy could be a common mechanism of neurodegeneration. 5289: 1445:

In another experiment using a rat model of Alzheimer's disease, it was demonstrated that systemic administration of hypothalamic proline-rich peptide (PRP)-1 offers neuroprotective effects and can prevent neurodegeneration in hippocampus

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have been observed in many different neurodegenerative diseases. This suggests that defective axons are not only present in diseased neurons, but also that they may cause certain pathological insult due to accumulation of organelles.

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at low concentrations, or aponecrosis (combination of apoptosis and necrosis) at higher concentrations. It is still unclear exactly what combination of apoptosis, non-apoptosis, and necrosis causes different kinds of aponecrosis.

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by α-secretase rather than β-secretase, the toxic protein β amyloid is not produced. Targeted inhibition of β-secretase can potentially prevent the neuronal death that is responsible for the symptoms of Alzheimer's disease.

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Galoyan AA, Sarkissian JS, Chavushyan VA, Meliksetyan IB, Avagyan ZE, Poghosyan MV, et al. (September 2008). "Neuroprotection by hypothalamic peptide proline-rich peptide-1 in Abeta25-35 model of Alzheimer's disease".

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is to enhance aspects of the immune system. Both active and passive vaccinations have been proposed for Alzheimer's disease and other conditions; however, more research must be done to prove safety and efficacy in humans.

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Hill-Burns, Erin M.; Debelius, Justine W.; Morton, James T.; Wissemann, William T.; Lewis, Matthew R.; Wallen, Zachary D.; Peddada, Shyamal D.; Factor, Stewart A.; Molho, Eric; Zabetian, Cyrus P.; Knight, Rob (May 2017).

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is a form of programmed cell death in multicellular organisms. It is one of the main types of programmed cell death (PCD) and involves a series of biochemical events leading to a characteristic cell morphology and death.

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defects may also lead to neurodegeneration. Research has shown that mutant proteins bind to the CMA-pathway receptors on lysosomal membrane and in doing so block their own degradation as well as the degradation of other

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Nabais, Marta F.; Laws, Simon M.; Lin, Tian; Vallerga, Costanza L.; Armstrong, Nicola J.; Blair, Ian P.; Kwok, John B.; Mather, Karen A.; Mellick, George D.; Sachdev, Perminder S.; Wallace, Leanne (2021-03-26).

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Levine, Kristin S.; Leonard, Hampton L.; Blauwendraat, Cornelis; Iwaki, Hirotaka; Johnson, Nicholas; Bandres-Ciga, Sara; Ferrucci, Luigi; Faghri, Faraz; Singleton, Andrew B.; Nalls, Mike A. (19 January 2023).

389:, which initiates and modulates motion. The weaker signals from subthalamic nuclei thus cause reduced initiation and modulation of movement, resulting in the characteristic movements of the disorder, notably 5798: 940:

The tubes formed from these lipid vesicles consist of both micellar as well as bilayer tubes. Extensive induction of membrane curvature is deleterious to the cell and would eventually lead to cell death.

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Barnat, Monia; Capizzi, Mariacristina; Aparicio, Esther; Boluda, Susana; Wennagel, Doris; Kacher, Radhia; Kassem, Rayane; Lenoir, Sophie; Agasse, Fabienne; Braz, Barbara Y.; Liu, Jeh-Ping (2020-08-14).

1050:, could lead to accumulation of DNA damage with age and contribute to brain aging and neurodegeneration. DNA single-strand breaks are common and are associated with the neurodegenerative disease ataxia- 668:, most of which are located in completely unrelated genes. In many of the different diseases, the mutated gene has a common feature: a repeat of the CAG nucleotide triplet. CAG codes for the amino acid 890:

Decreased proteasome activity is consistent with models in which intracellular protein aggregates form. It is still unknown whether or not these aggregates are a cause or a result of neurodegeneration.

6184: 6179: 972:) is a central feature of all neurodegenerative disorders. In addition to the generation of ROS, mitochondria are also involved with life-sustaining functions including calcium homeostasis, PCD, 850:

Parkinson's disease and Huntington's disease are both late-onset and associated with the accumulation of intracellular toxic proteins. Diseases caused by the aggregation of proteins are known as

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The most common form of cell death in neurodegeneration is through the intrinsic mitochondrial apoptotic pathway. This pathway controls the activation of caspase-9 by regulating the release of

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There is strong evidence that mitochondrial dysfunction and oxidative stress play a causal role in neurodegenerative disease pathogenesis, including in four of the more well known diseases

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Svob Strac, Dubravka; Konjevod, Marcela; Sagud, Marina; Nikolac Perkovic, Matea; Nedic Erjavec, Gordana; Vuic, Barbara; Simic, Goran; Vukic, Vana; Mimica, Ninoslav; Pivac, Nela (2021).

4584:"Chronic oxidative damage together with genome repair deficiency in the neurons is a double whammy for neurodegeneration: Is damage response signaling a potential therapeutic target?" 964:(ROS) are normal byproducts of mitochondrial respiratory chain activity. ROS concentration is mediated by mitochondrial antioxidants such as manganese superoxide dismutase (SOD2) and 5163:

Esch FS, Keim PS, Beattie EC, Blacher RW, Culwell AR, Oltersdorf T, et al. (June 1990). "Cleavage of amyloid beta peptide during constitutive processing of its precursor".

518:. The specific mechanism of toxicity still needs to be investigated, but the findings are significant because they implicate cells other than neuron cells in neurodegeneration. 625: 775:. Alpha-synuclein is the primary structural component of Lewy body fibrils. In addition, an alpha-synuclein fragment, known as the non-Abeta component (NAC), is found in 4946:

Caccamo D, Currò M, Condello S, Ferlazzo N, Ientile R (February 2010). "Critical role of transglutaminase and other stress proteins during neurodegenerative processes".

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The consequences of neurodegeneration can vary widely depending on the specific region affected, ranging from issues related to movement to the development of dementia.

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Quinn C, Edmundson C, Dahodwala N, Elman L (April 2020). "Reliable and efficient scale to assess upper motor neuron disease burden in amyotrophic lateral sclerosis".

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Turner PR, O'Connor K, Tate WP, Abraham WC (May 2003). "Roles of amyloid precursor protein and its fragments in regulating neural activity, plasticity and memory".

1197:. Initiator caspases cleave inactive forms of effector caspases. This activates the effectors that in turn cleave other proteins resulting in apoptotic initiation. 902:(PCD), this becomes the favorable route when a protein is aggregate-prone meaning it is a poor proteasome substrate. This can be split into two forms of autophagy: 5120:

Pastorino L, Ikin AF, Lamprianou S, Vacaresse N, Revelli JP, Platt K, et al. (April 2004). "BACE (beta-secretase) modulates the processing of APLP2 in vivo".

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studies often use a variety of animal models because there is such a clearly defined trigger – repeat expansion. Extensive research has been done using the

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allele to the onset of MS – they may contribute to the degree of autoimmune attack and the resultant inflammation – they do not determine the onset of MS.

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of these proteins and peptides make them clump together. The resulting structures are turned extremely resistant to chemical and mechanical disruption.

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disease that is characterized by rapidly progressive dementia. Misfolded proteins called prions aggregate in brain tissue leading to nerve cell death.

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Tiraboschi P, Hansen LA, Thal LJ, Corey-Bloom J (June 2004). "The importance of neuritic plaques and tangles to the development and evolution of AD".

1063: 1059: 659: 3746: 6156: 5333: 833: 1635: 6277: 6136: 5809: 1055: 573: 6161: 5793: 3886: 3123: 2813: 2751:"Parkinson's disease and Parkinson's disease medications have distinct signatures of the gut microbiome: PD, Medications, and Gut Microbiome" 2153: 2065: 2033: 6938: 5999: 5987: 5449: 246:

that penetrates through the neuron's membrane. APP appears to play roles in normal neuron growth, survival and post-injury repair. APP is

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Estrada Sánchez AM, Mejía-Toiber J, Massieu L (April 2008). "Excitotoxic neuronal death and the pathogenesis of Huntington's disease".

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Hooper NM (April 2005). "Roles of proteolysis and lipid rafts in the processing of the amyloid precursor protein and prion protein".

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It has been proved that in these neurodegenerative diseases (Alzheimer's disease, Parkinson's disease, and Huntington's disease) the

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endoplasmic reticulum (ER), (as seen with neuroserpin mutations that cause familial encephalopathy with neuroserpin inclusion bodies)

262:. One of these fragments gives rise to fibrils of amyloid beta which can self-assemble into the dense extracellular amyloid plaques. 6785: 5921: 5724: 3606:

Johnson, Tyler B.; Cain, Jacob T.; White, Katherine A.; Ramirez-Montealegre, Denia; Pearce, David A.; Weimer, Jill M. (March 2019).

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is a rare and fatal recessive neurodegenerative disorder that begins in childhood. Batten disease is the common name for a group of

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might play a role in the diagnosis of PD, and research suggests various ways that could revolutionize the future of PD treatment.

1662:"Whole-Brain Dynamics Disruptions in the Progression of Alzheimer's Disease: Understanding the Influence of Amyloid-Beta and Tau" 1034: 613: 577: 4097: 1707:"The Emerging Scenario of the Gut-Brain Axis: The Therapeutic Actions of the New Actor Kefir against Neurodegenerative Diseases" 404:

in neurons, and may be directly toxic. Additionally, they may damage molecular motors and microtubules to interfere with normal

6928: 6040: 1586:"A Review of the Common Neurodegenerative Disorders: Current Therapeutic Approaches and the Potential Role of Nanotherapeutics" 6923: 5555: 5531: 5361: 540: 174:

Comparison of brain tissue between healthy individual and Alzheimer's disease patient, demonstrating extent of neuronal death

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The presence of epigenetic modifications for certain genes has been demonstrated in this type of pathology. An example is

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Nine inherited neurodegenerative diseases are caused by the expansion of the CAG trinucleotide and polyQ tract, including

677: 655: 641:) viral exposures can significantly elevate risks of neurodegenerative disease, including up to 15 years after infection. 472: 467: 104: 6780: 6601: 6203: 5577: 604: 1156:

Occur when factors outside the cell activate cell surface death receptors (e.g., Fas) that result in the activation of

6820: 5713: 449:, causing an autoimmune response. This sets off a cascade of signaling molecules that result in T cells, B cells, and 6347: 6270: 6191: 5741: 5413: 1705:

Pereira, TMC; Côco, LZ; Ton, AMM; Meyrelles, SS; Campos-Toimil, M; Campagnaro, BP; Vasquez, EC (20 November 2021).

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The process of neurodegeneration is not well understood, so the diseases that stem from it have, as yet, no cures.

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Apart from tubular structures, alpha-synuclein can also form lipoprotein nanoparticles similar to apolipoproteins.

6790: 6659: 6141: 6109: 5910: 768: 560: 239: 4393:"Meta-analysis of genome-wide DNA methylation identifies shared associations across neurodegenerative disorders" 3826:

Lin MT, Beal MF (October 2006). "Mitochondrial dysfunction and oxidative stress in neurodegenerative diseases".

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De Vos KJ, Grierson AJ, Ackerley S, Miller CC (2008). "Role of axonal transport in neurodegenerative diseases".

2020: 6754: 6729: 6654: 6561: 6466: 6362: 6208: 5982: 5396: 5308: 2233:"[P2–430]: Accuracy of Clinical Diagnosis of Alzheimer's Disease in Alzheimer's Disease Centers (ADCS)" 1899:

Rubinsztein DC (October 2006). "The roles of intracellular protein-degradation pathways in neurodegeneration".

634: 6213: 2699:"Invalid Self-Assessment of Olfactory Functioning in Parkinson's Disease Patients May Mislead the Neurologist" 400:

expansion in the huntingtin gene, resulting in the mutant huntingtin. Aggregates of mutant huntingtin form as

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within affected neurons. It is thought that defects in protein transport machinery and regulation, such as

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in which a cell actively consumes damaged organelles or misfolded proteins by encapsulating them into an

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Kaufman, David Myland; Milstein, Mark J. (2013-01-01), Kaufman, David Myland; Milstein, Mark J. (eds.),

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protein aggregates have been implicated in some cases of the disease, and a mutation in chromosome 9 (

6870: 6621: 6461: 6432: 6327: 6030: 5847: 5736: 5172: 4188: 4065: 3835: 3269: 3087:"Multiple Sclerosis: Hope Through Research | National Institute of Neurological Disorders and Stroke" 2990: 1976: 1908: 980:, lipid concentration of the mitochondrial membranes, and the mitochondrial permeability transition. 977: 442: 4530:"Oxidative Stress in Neurodegenerative Diseases: From Molecular Mechanisms to Clinical Applications" 3218: 1285:

Each of these neurodegenerative diseases have one (or several) specific main protein or peptide. In

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Vila M, Przedborski S (May 2003). "Targeting programmed cell death in neurodegenerative diseases".

2594:"Membrane curvature induction and tubulation are common features of synucleins and apolipoproteins" 1409: 1395: 1279: 1062:. Defective DNA repair has been linked to neurodegenerative disorders such as Alzheimer's disease, 984:

leading to neurodegeneration is likely, at least on some level, to involve all of these functions.

792: 746: 673: 446: 397: 382: 362: 4290:"Unstable nucleotide repeat minireview series: a molecular biography of unstable repeat disorders" 3365:"Astrocytes expressing ALS-linked mutated SOD1 release factors selectively toxic to motor neurons" 6840: 6734: 6674: 6397: 6377: 6129: 6114: 6102: 5852: 5803: 5640: 5503: 5391: 5145: 5053: 4971: 4862: 4214: 4089: 3859: 3728: 3549: 3345: 2645:"Variants in GBA, SNCA, and MAPT influence Parkinson disease risk, age at onset, and progression" 2481: 2424: 2346: 2254: 1932: 1106: 1051: 484: 480: 426: 421: 351: 322: 108: 5325: 3747:"Creutzfeldt-Jakob Disease Fact Sheet | National Institute of Neurological Disorders and Stroke" 1178:

are other organelles that have damage sensors, which can lead the cells down apoptotic pathways.

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Masten MC, Williams JD, Vermilion J, Adams HR, Vierhile A, Collins A, et al. (June 2020).

3414:"Non-cell autonomous effect of glia on motor neurons in an embryonic stem cell-based ALS model" 6759: 6694: 6669: 6521: 6481: 5892: 5858: 5830: 5821: 5753: 5729: 5596: 5444: 5239: 5188: 5137: 5102: 5045: 4963: 4911: 4854: 4819: 4768: 4719: 4665: 4613: 4561: 4510: 4475: 4424: 4372: 4321: 4270: 4206: 4154: 4081: 4037: 3982: 3933: 3882: 3851: 3693: 3637: 3541: 3500: 3482: 3443: 3394: 3337: 3295: 3233: 3182: 3119: 3065: 3016: 2955: 2895: 2846: 2809: 2780: 2730: 2674: 2625: 2569: 2516: 2499:

Elbaz A, Carcaillon L, Kab S, Moisan F (January 2016). "Epidemiology of Parkinson's disease".

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There are two main avenues eukaryotic cells use to remove troublesome proteins or organelles:

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Nagai M, Re DB, Nagata T, Chalazonitis A, Jessell TM, Wichterle H, Przedborski S (May 2007).

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Purves D, Augustine GA, Fitzpatrick D, Hall W, LaMantia AS, McNamara JO, Williams SM (2001).

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Wang H, Dharmalingam P, Vasquez V, Mitra J, Boldogh I, Rao KS, et al. (January 2017).

4506: 2565: 6860: 6855: 6850: 6845: 6739: 6679: 6616: 6531: 6491: 6476: 6427: 6417: 6372: 5937: 5628: 3799:"Variant Creutzfeldt-Jakob Disease (vCJD) and Factor VIII (pdFVIII) Questions and Answers" 1429: 1405: 1387: 1381: 1366: 1333: 1302: 1265: 1261: 1257: 1175: 1093: 776: 758: 750: 386: 355: 299: 255: 223: 216: 196: 2660: 2643:

Davis AA, Andruska KM, Benitez BA, Racette BA, Perlmutter JS, Cruchaga C (January 2016).

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or endoplasmic reticulum malfunctions, each leading to the activation of caspase-9. The

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disease, is a rare neurodegenerative disorder characterized by the gradual loss of both

238:(also written as A-beta or Aβ). Amyloid beta is a fragment from a larger protein called 150:

Within neurodegenerative diseases, it is estimated that 55 million people worldwide had

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advances against one neurodegenerative disease might ameliorate other diseases as well.

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Varkey J, Isas JM, Mizuno N, Jensen MB, Bhatia VK, Jao CC, et al. (October 2010).

2412: 2298: 2273: 2205: 2178: 1997: 1964: 1833: 1806: 1782: 1757: 1733: 1706: 1612: 1585: 1561: 1534: 1353: 1298: 1253: 1133: 992: 988: 904: 829: 736: 685: 576:(vCJD) is the infectious form that comes from the meat of a cow that was infected with 532: 527: 330: 259: 212: 132: 2866:"Glial cells as intrinsic components of non-cell-autonomous neurodegenerative disease" 2697:

Schmidt, Nele; Paschen, Laura; Witt, Karsten (2020-11-16). Mirabella, Giovanni (ed.).

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to each other and potentially to any other transglutaminase substrate in the brain.

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can aggregate to form insoluble fibrils in pathological conditions characterized by

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gene, which progressively increases its expression with age and has been related to

6835: 6830: 6714: 6546: 6471: 6422: 6412: 6387: 6382: 6352: 6286: 5516: 5386: 5369: 3863: 3608:"Therapeutic landscape for Batten disease: current treatments and future prospects" 3553: 3167: 2289: 2060:. Focus on structural biology. Dordrecht, Netherlands, New York, London: Springer. 1936: 1479: 1447: 1433: 1325: 1290: 1242: 1206: 1171: 1167: 1114: 1110: 953: 814: 753:. Protein toxicity is one of the key mechanisms of many neurodegenrative diseases. 374: 366: 287: 280: 235: 2534: 1584:

Lamptey RN, Chaulagain B, Trivedi R, Gothwal A, Layek B, Singh J (February 2022).

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The main known risk factor is age. Mutations in genes such as α-synuclein (SNCA),

61:

on left contrasted with structural changes shown in brain on right of person with

5313: 5000:

Sweetlove M (2012). "Phase III CONCERT Trial of Latrepirdine. Negative results".

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510:

evidence that the primary cellular sites where SOD1 mutations act are located on

17: 6704: 6551: 5475: 5436: 5378: 5224: 3919: 3478: 2249: 2232: 1552: 1018: 803: 795: 787: 764: 742: 594: 326: 307: 247: 136: 58: 5041: 4409: 4077: 3281: 3051: 2799: 1396:

abnormal structures that are characteristic of these neurodegenerative diseases

1137:

alternatively, PCD may occur in response to other injury or disease processes.

942: 939: 170: 6865: 6566: 5586: 5456: 5133: 4959: 4599: 4460: 3902:

Maynard S, Fang EF, Scheibye-Knudsen M, Croteau DL, Bohr VA (September 2015).

3623: 3202:"Remyelination protects axons from demyelination-associated axon degeneration" 2459: 2274:"Synapse formation and function is modulated by the amyloid precursor protein" 1823: 1673: 1337: 1310: 1186: 1117:. When axonal transport is severely disrupted a degenerative pathway known as 1047: 638: 496: 476: 450: 100: 79: 4882:"Pharmacological manipulation of cell death: clinical applications in sight?" 4493:

DiMauro S, Schon EA (2008). "Mitochondrial disorders in the nervous system".

3486: 3036:"Huntington's disease: underlying molecular mechanisms and emerging concepts" 2163: 2101: 1535:"Clinical Neurology and Epidemiology of the Major Neurodegenerative Diseases" 6810: 6501: 5696: 5647: 5635: 5618: 5550: 5302: 5298: 5184: 4006:"Virus exposure and neurodegenerative disease risk across national biobanks" 3968: 3724: 3002: 2610: 2093: 1660:

Patow, Gustavo; Escrichs, Anira; Ritter, Petra; Deco, Gustavo (2024-03-31).

1412:

has been detected in the autopsy of brains of patients with these diseases.

1278:

Most relevant human neurodegenerative diseases share the property of having

1145: 883: 669: 511: 303: 128: 75: 5243: 5141: 5106: 5049: 4967: 4915: 4858: 4823: 4772: 4723: 4669: 4617: 4565: 4546: 4514: 4479: 4428: 4376: 4357: 4325: 4306: 4274: 4255: 4210: 4158: 4085: 4041: 3986: 3937: 3855: 3697: 3641: 3545: 3504: 3447: 3398: 3341: 3299: 3237: 3228: 3201: 3186: 3069: 3020: 2959: 2899: 2850: 2784: 2734: 2715: 2678: 2629: 2573: 2520: 2477: 2420: 2385: 2342: 2307: 2214: 2128: 2006: 1928: 1842: 1791: 1742: 1723: 1691: 1621: 1570: 854:, and they are primarily caused by aggregates in the following structures: 154:

in 2019, and that by 2050 this figure will increase to 139 million people.

5192: 4123:"Viruses in neurodegenerative diseases: More than just suspects in crimes" 2179:"Personalizing the Care and Treatment of Alzheimer's Disease: An Overview" 2143: 2081: 491:

were discovered in a subset of patients with familial ALS. More recently,

6719: 5876: 5868: 5834: 5688: 5591: 5261: 2195: 1602: 1223: 1182: 1157: 689: 548: 544: 370: 295: 151: 5281: 4788:"Bacterial programmed cell death and multicellular behavior in bacteria" 3847: 1988: 1920: 187:(AD) is a chronic neurodegenerative disease that results in the loss of 5013: 3536: 3519: 2377: 1533:

Erkkinen, Michael G.; Kim, Mee-Ohk; Geschwind, Michael D (April 2018).

1495: 1438: 1239: 1102: 500: 251: 231: 200: 192: 144: 3333: 2766: 1773: 871:

extracellularly excreted proteins, amyloid-beta in Alzheimer's disease

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Engelberg-Kulka H, Amitai S, Kolodkin-Gal I, Hazan R (October 2006).

4053:"Massive health-record review links viral illnesses to brain disease" 3412:

Di Giorgio FP, Carrasco MA, Siao MC, Maniatis T, Eggan K (May 2007).

3256:

Min YG, Choi SJ, Hong YH, Kim SM, Shin JY, Sung JJ (September 2020).

1450:

25–35. This suggests that there could be therapeutic value to PRP-1.

1373: 1006: 727:

and increased tau pathology both in vitro and in mouse models of AD.

600: 492: 390: 188: 92: 4850: 4239:"Animal models of polyglutamine diseases and therapeutic approaches" 4201: 4176: 6442: 6171:

Spinal muscular atrophy with lower extremity predominance (SMALED)

3429: 3380: 2881: 5073:"Active and passive immunotherapy for neurodegenerative disorders" 2145:

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Wenk GL (2003). "Neuropathologic changes in Alzheimer's disease".

1038: 823: 720: 569: 318: 169: 1807:"Oxidative Stress: A Key Modulator in Neurodegenerative Diseases" 1101:

can be disrupted by a variety of mechanisms including damage to:

1054:. Increased oxidative DNA damage in the brain is associated with 1029:

The brain metabolizes as much as a fifth of consumed oxygen, and

3116:

Kaufman's Clinical Neurology for Psychiatrists (Seventh Edition)

1252:

proteins and peptides intra- and intermolecularly, by a type of

488: 409: 311: 6259: 6255: 5329: 3998: 3996: 3797:

Research, Center for Biologics Evaluation and (12 April 2019).

1756:

Stephenson, J; Nutma, E; van der Valk, P; Amor, S (June 2018).

4444:"Mechanisms of protein toxicity in neurodegenerative diseases" 2022:

Global status report on the public health response to dementia

1329: 1294: 1042: 819:

the major component of amyloid plaques in Alzheimer's disease.

802:

in Alzheimer's disease; tau fibrils are the main component of

637:

indicates that 45 (with 22 of these being replicated with the

298:. The cause of this selective cell death is unknown. Notably, 408:, leading to impaired transport of important cargoes such as 369:. The first brain region to be substantially affected is the 1013:

due to their strong metabolic activity associated with high

1805:

Singh, A; Kukreti, R; Saso, L; Kukreti, S (22 April 2019).

1185:(cysteine-aspartic acid proteases) cleave at very specific 599:

The greatest risk factor for neurodegenerative diseases is

222:

AD pathology is primarily characterized by the presence of

3953:"Brain metabolism in health, aging, and neurodegeneration" 2058:

Protein folding and misfolding: neurodegenerative diseases

1245:

present in the human body and in the brain in particular.

143:) and induced cell death. These similarities suggest that 629:

Risks from viral exposures according to one biobank study

2444:"Amyloid fibrils from the viewpoint of protein folding" 1033:

produced by oxidative metabolism are a major source of

676:. Diseases associated with such mutations are known as 306:

complexes and aggregates are observed to accumulate in

199:

and certain subcortical structures, resulting in gross

4528:

Liu Z, Zhou T, Ziegler AC, Dimitrion P, Zuo L (2017).

3904:"DNA Damage, DNA Repair, Aging, and Neurodegeneration" 1428:

In the search for effective treatments (as opposed to

354:

neurodegenerative disorder caused by mutations in the

99:. Neuronal damage may also ultimately result in their 3151:"Recent advances in understanding multiple sclerosis" 741:

Several neurodegenerative diseases are classified as

234:, typically 39–43 amino acids in length, called 5271: 2979:"Huntington's disease alters human neurodevelopment" 2808:(2nd ed.). Sunderland, MA: Sinauer Associates. 1437:

ameliorate disease severity. An example is the drug

1280:

abnormal structures made up of proteins and peptides

6773: 6635: 6575: 6450: 6311: 6092: 6069: 6060: 6053: 6008: 5958: 5930: 5901: 5867: 5829: 5818: 5784: 5762: 5687: 5497: 5488: 5474: 5434: 5377: 5368: 5275: 4237:Marsh JL, Lukacsovich T, Thompson LM (March 2009). 139:level, including atypical protein assemblies (like 69: 42: 5208:"Treatment strategies targeting amyloid β-protein" 4051: 5206:Schenk D, Basi GS, Pangalos MN (September 2012). 4121:Leblanc, Pascal; Vorberg, Ina Maja (2022-08-04). 3773:"Creutzfeldt-Jakob disease - Symptoms and causes" 3118:, Philadelphia: W.B. Saunders, pp. 329–349, 514:. Astrocytes then cause the toxic effects on the 3081: 3079: 1758:"Inflammation in CNS neurodegenerative diseases" 4688:Jeppesen DK, Bohr VA, Stevnsner T (July 2011). 4683: 4681: 4679: 4636:"DNA damage and its links to neurodegeneration" 4629: 4627: 4577: 4575: 3881:. San Diego: Academic Press. pp. 121–139. 3149:Stys, Peter K.; Tsutsui, Shigeki (2019-12-13). 2692: 2690: 2688: 3657: 3655: 3653: 3651: 2971: 2969: 2226: 2224: 1963:Bredesen DE, Rao RV, Mehlen P (October 2006). 1506:Neurodegeneration with brain iron accumulation 1482:for patients who are suffering from a serious 664:Many neurodegenerative diseases are caused by 6271: 5341: 4442:Chung, CG; Lee, H; Lee, SB (September 2018). 3520:"ALS: astrocytes move in as deadly neighbors" 3461:Phatnani, Hemali; Maniatis, Tom (June 2015). 3315: 3313: 3311: 3309: 1894: 1892: 1890: 1888: 1886: 1884: 1882: 1880: 1878: 1528: 1526: 1404:Co-localization of transglutaminase mediated 887:primary route cells use to degrade proteins. 8: 6806:Intraoperative neurophysiological monitoring 4690:"DNA repair deficiency in neurodegeneration" 3601: 3599: 3597: 3595: 3593: 3591: 3144: 3142: 3140: 2587: 2585: 2583: 2533:"Parkinson's Disease Mechanism Discovered," 5212:Cold Spring Harbor Perspectives in Medicine 4739:"Wallerian degeneration, wld(s), and nmnat" 4170: 4168: 3908:Cold Spring Harbor Perspectives in Medicine 3711:Hartnett L (2019-09-30). "Batten disease". 3251: 3249: 3247: 2864:Lobsiger CS, Cleveland DW (November 2007). 2028:. Geneva: World Health Organization. 2021. 1958: 1956: 1954: 1952: 1950: 1948: 1946: 1189:residues. There are two types of caspases: 65:, the most common neurodegenerative disease 6278: 6264: 6256: 6066: 6057: 5826: 5494: 5485: 5374: 5348: 5334: 5326: 5272: 4941: 4939: 4937: 4935: 4933: 4931: 4929: 4927: 4925: 4634:Madabhushi R, Pan L, Tsai LH (July 2014). 4177:"Neurodegeneration: a question of balance" 3467:Cold Spring Harbor Perspectives in Biology 2930:"Functional anatomy of movement disorders" 2800:"Circuits within the Basal Ganglia System" 2183:Pharmacogenomics and Personalized Medicine 1540:Cold Spring Harbor Perspectives in Biology 1348:in vitro or in vivo, that is, they can be 1248:The main function of transglutaminases is 1017:levels, high oxygen consumption, and weak 858:cytosol, e.g. Parkinson's and Huntington's 808:behavioral variant frontotemporal dementia 286:PD is primarily characterized by death of 48: 39: 5233: 5223: 5096: 4905: 4813: 4803: 4762: 4713: 4659: 4607: 4555: 4545: 4534:Oxidative Medicine and Cellular Longevity 4469: 4459: 4418: 4408: 4366: 4356: 4315: 4305: 4264: 4254: 4200: 4148: 4138: 4031: 4021: 3976: 3927: 3687: 3631: 3535: 3494: 3463:"Astrocytes in Neurodegenerative Disease" 3437: 3388: 3289: 3227: 3217: 3176: 3166: 3059: 3010: 2949: 2889: 2774: 2724: 2714: 2668: 2619: 2609: 2467: 2297: 2248: 2204: 2194: 1996: 1832: 1822: 1781: 1732: 1722: 1681: 1611: 1601: 1560: 660:Epigenetics of neurodegenerative diseases 4232: 4230: 4228: 3200:Irvine, K. A.; Blakemore, W. F. (2008). 2547: 2545: 2543: 624: 3034:Labbadia J, Morimoto RI (August 2013). 1522: 834:transmissible spongiform encephalopathy 6137:Distal hereditary motor neuronopathies 5810:Template:Demyelinating diseases of CNS 5089:10.1146/annurev.neuro.31.060407.125529 4507:10.1146/annurev.neuro.30.051606.094302 3821: 3819: 3565: 3563: 2912: 2566:10.1146/annurev.neuro.31.061307.090711 2231:Archer MC, Hall PH, Morgan JC (2017). 4886:The Journal of Clinical Investigation 3951:Camandola S, Mattson MP (June 2017). 1205:Autophagy is a form of intracellular 1166:Result from mitochondrial release of 103:. Neurodegenerative diseases include 91:is caused by the progressive loss of 7: 6896: 5988:Idiopathic intracranial hypertension 5122:Molecular and Cellular Neurosciences 4989:Dimebon Disappoints in Phase 3 Trial 4880:Green DR, Kroemer G (October 2005). 4588:Mechanisms of Ageing and Development 4448:Cellular and Molecular Life Sciences 4100:from the original on 6 February 2023 2661:10.1016/j.neurobiolaging.2015.09.014 2448:Cellular and Molecular Life Sciences 2056:Ovádi, Judit; Orosz, Ferenc (2009). 1857:"What is Neurodegenerative Disease?" 1394:reaction) have been detected in the 4755:10.1146/annurev-neuro-060909-153248 4345:The Journal of Biological Chemistry 4294:The Journal of Biological Chemistry 4243:The Journal of Biological Chemistry 2942:10.1046/j.1469-7580.2000.19640519.x 2598:The Journal of Biological Chemistry 493:TAR DNA-binding protein 43 (TDP-43) 439:myelin oligodendrocyte glycoprotein 6219:Infantile progressive bulbar palsy 2442:Ohnishi S, Takano K (March 2004). 2413:10.1212/01.WNL.0000129697.01779.0A 2117:The Journal of Clinical Psychiatry 1965:"Cell death in the nervous system" 910:chaperone-mediated autophagy (CMA) 373:, followed by degeneration of the 25: 6786:Development of the nervous system 5922:Template:Cerebrovascular diseases 5725:Frontotemporal lobar degeneration 3877:Bernstein C, Bernstein H (1991). 3112:"Chapter 15 - Multiple Sclerosis" 958:mitochondrial intermembrane space 700:), mice, and non-human primates. 574:Variant Creutzfeldt–Jakob disease 361:. HD is characterized by loss of 6895: 6884: 6883: 6441: 5942:For more detailed coverage, see 5920:For more detailed coverage, see 5891:For more detailed coverage, see 5857:For more detailed coverage, see 5808:For more detailed coverage, see 4339:Zoghbi HY, Orr HT (March 2009). 2366:Biochemical Society Transactions 2086:Cell Biochemistry and Biophysics 745:as they are associated with the 578:bovine spongiform encephalopathy 4737:Coleman MP, Freeman MR (2010). 4706:10.1016/j.pneurobio.2011.04.013 4050:Kozlov, Max (23 January 2023). 1009:are particularly vulnerable to 767:, such as Parkinson's disease, 672:. A repeat of CAG results in a 580:, also called mad cow disease. 429:(MS) is a chronic debilitating 230:. Plaques are made up of small 5071:Brody DL, Holtzman DM (2008). 4048:News article about the study: 3753:. National Institute of Health 3168:10.12688/f1000research.20906.1 3040:Trends in Biochemical Sciences 2290:10.1523/JNEUROSCI.1450-06.2006 2148:. Princeton University Press. 1474:Dr. Antonio Barbera, a former 1459:only beginning to understand. 1454:Other avenues of investigation 678:trinucleotide repeat disorders 541:neuronal ceroid lipofuscinoses 506:Independent research provided 27:Central nervous system disease 1: 6627:Social cognitive neuroscience 6235:Amyotrophic lateral sclerosis 6120:Hereditary spastic paraplegia 5978:Normal pressure hydrocephalus 5077:Annual Review of Neuroscience 4495:Annual Review of Neuroscience 2554:Annual Review of Neuroscience 2335:10.1016/S0301-0082(03)00089-3 1164:Intrinsic apoptotic pathways: 1154:Extrinsic apoptotic pathways: 1064:amyotrophic lateral sclerosis 1046:decline in the activities of 1001:amyotrophic lateral sclerosis 863:Spinocerebellar ataxia type 1 656:Trinucleotide repeat disorder 489:superoxide dismutase 1 (SOD1) 473:Amyotrophic lateral sclerosis 468:Amyotrophic lateral sclerosis 462:Amyotrophic lateral sclerosis 105:amyotrophic lateral sclerosis 30:For the medical journal, see 6602:Molecular cellular cognition 6204:Progressive muscular atrophy 4839:Nature Reviews. Neuroscience 4805:10.1371/journal.pgen.0020135 4652:10.1016/j.neuron.2014.06.034 4140:10.1371/journal.ppat.1010670 4023:10.1016/j.neuron.2022.12.029 3713:Learning Disability Practice 3680:10.1212/WNL.0000000000009454 2843:10.1016/j.arcmed.2007.11.011 2831:Archives of Medical Research 2513:10.1016/j.neurol.2015.09.012 923:chaperone-mediated autophagy 896:autophagy–lysosome pathways: 846:Protein degradation pathways 475:(ALS), commonly referred to 385:send control signals to the 319:leucine-rich repeat kinase 2 6939:Neurodegenerative disorders 6821:Neurodevelopmental disorder 6796:Neural network (biological) 6791:Neural network (artificial) 5714:Primary progressive aphasia 5225:10.1101/cshperspect.a006387 3920:10.1101/cshperspect.a025130 3479:10.1101/cshperspect.a020628 2936:. 196 ( Pt 4) (4): 519–25. 2917:Box A. Huntington's Disease 2278:The Journal of Neuroscience 2250:10.1016/j.jalz.2017.06.1086 2142:Lock MM (27 October 2013). 1553:10.1101/cshperspect.a033118 1119:Wallerian-like degeneration 674:polyglutamine (polyQ) tract 605:Mitochondrial DNA mutations 537:lysosomal storage disorders 6955: 6348:Computational neuroscience 6036:Hashimoto's encephalopathy 5742:Posterior cortical atrophy 5563:Striatonigral degeneration 5414:Cavernous sinus thrombosis 5042:10.1016/j.jalz.2007.10.019 5030:Alzheimer's & Dementia 4410:10.1186/s13059-021-02275-5 4175:Thompson LM (April 2008). 4078:10.1038/d41586-023-00181-3 3879:Aging, Sex, and DNA Repair 3282:10.1038/s41598-020-72887-7 3052:10.1016/j.tibs.2013.05.003 2237:Alzheimer's & Dementia 1476:obstetrics and gynaecology 1085: 1074:, Parkinson's disease and 968:. Over production of ROS ( 734: 653: 592: 558: 525: 465: 419: 340: 269: 250:into smaller fragments by 177: 95:, in the process known as 29: 6879: 6816:Neurodegenerative disease 6660:Evolutionary neuroscience 6439: 6293: 6142:Spinal muscular atrophies 6110:Primary lateral sclerosis 5968:Intracranial hypertension 5748:Creutzfeldt–Jakob disease 5134:10.1016/j.mcn.2003.12.013 4960:10.1007/s00726-009-0428-3 4600:10.1016/j.mad.2016.09.005 4461:10.1007/s00018-018-2854-4 3624:10.1038/s41582-019-0138-8 2460:10.1007/s00018-003-3264-8 1824:10.3390/molecules24081583 1674:10.1101/2024.03.29.587333 1424:Animal models in research 948:Mitochondrial dysfunction 798:is the main component of 769:dementia with Lewy bodies 635:electronic health records 566:Creutzfeldt–Jakob disease 561:Creutzfeldt-Jakob disease 555:Creutzfeldt–Jakob disease 381:cortices. The striatum's 240:amyloid precursor protein 89:neurodegenerative disease 56: 47: 43:Neurodegenerative disease 6781:Brain–computer interface 6730:Neuromorphic engineering 6655:Educational neuroscience 6562:Nutritional neuroscience 6467:Clinical neurophysiology 6363:Integrative neuroscience 6209:Progressive bulbar palsy 6000:Intracranial hypotension 5983:Choroid plexus papilloma 5397:Herpesviral encephalitis 4694:Progress in Neurobiology 3612:Nature Reviews Neurology 2928:Crossman AR (May 2000). 2323:Progress in Neurobiology 1432:), investigators employ 841:Intracellular mechanisms 6592:Behavioral neuroscience 5721:Frontotemporal dementia 5407:Encephalitis lethargica 5185:10.1126/science.2111583 3969:10.15252/embj.201695810 3725:10.7748/ldp.22.5.22.s16 3003:10.1126/science.aax3338 2611:10.1074/jbc.M110.139576 2094:10.1007/12013.1559-0283 1478:doctor, is prescribing 1352:by trasglutaminases by 1340:have been proved to be 1260:, in a reaction termed 1031:reactive oxygen species 962:Reactive oxygen species 800:neurofibrillary tangles 773:multiple system atrophy 709:spinocerebellar ataxias 336: 265: 228:neurofibrillary tangles 165: 125:multiple system atrophy 6929:Neurological disorders 6587:Affective neuroscience 6368:Molecular neuroscience 6323:Behavioral epigenetics 6026:Hepatic encephalopathy 4358:10.1074/jbc.R800041200 4307:10.1074/jbc.R800067200 4256:10.1074/jbc.R800065200 3518:Julien JP (May 2007). 1724:10.3390/antiox10111845 1511:Prevention of dementia 1217:Cytoplasmic (type III) 966:glutathione peroxidase 630: 497:Fused in Sarcoma (FUS) 435:central nervous system 175: 32:Experimental Neurology 6924:Clinical neuroscience 6650:Cultural neuroscience 6645:Consumer neuroscience 6487:Neurogastroenterology 6343:Cellular neuroscience 6084:Ataxia–telangiectasia 6041:Static encephalopathy 5764:Mitochondrial disease 5602:Spasmodic torticollis 5512:Basal ganglia disease 4288:Orr HT (March 2009). 2802:. In Purves D (ed.). 2649:Neurobiology of Aging 2243:(7S_Part_16): 800–1. 1668:: 2024.03.29.587333. 1484:neurological disorder 1363:augmented expression: 1130:Programmed cell death 1125:Programmed cell death 1092:Axonal swelling, and 1076:xeroderma pigmentosum 1068:ataxia telangiectasia 1041:. Damage to a cell's 982:Mitochondrial disease 974:mitochondrial fission 900:programmed cell death 880:ubiquitin–proteasome: 628: 593:Further information: 431:demyelinating disease 244:transmembrane protein 173: 6622:Sensory neuroscience 6462:Behavioral neurology 6433:Systems neuroscience 6031:Toxic encephalopathy 5737:Lewy bodies dementia 4547:10.1155/2017/2525967 3229:10.1093/brain/awn080 2716:10.1155/2020/7548394 2196:10.2147/PGPM.S284615 1603:10.3390/ijms23031851 1384:in these structures: 1201:Autophagic (type II) 1132:(PCD) is death of a 1121:is often triggered. 705:Huntington's disease 443:myelin basic protein 363:medium spiny neurons 348:Huntington's disease 343:Huntington's disease 337:Huntington's disease 121:Huntington's disease 6765:Social neuroscience 6665:Global neurosurgery 6542:Neurorehabilitation 6512:Neuro-ophthalmology 6497:Neurointensive care 6328:Behavioral genetics 6079:Friedreich's ataxia 5462:Meningoencephalitis 5402:Limbic encephalitis 5264:. January 12, 2024. 5177:1990Sci...248.1122E 4193:2008Natur.452..707T 4070:2023Natur.614...18K 3848:10.1038/nature05292 3840:2006Natur.443..787L 3674:(23): e2436–e2440. 3524:Nature Neuroscience 3418:Nature Neuroscience 3369:Nature Neuroscience 3274:2020NatSR..1015661M 2995:2020Sci...369..787B 2870:Nature Neuroscience 2703:Parkinson's Disease 2082:"Journal home page" 1989:10.1038/nature05293 1981:2006Natur.443..796B 1921:10.1038/nature05291 1913:2006Natur.443..780R 1410:abnormal structures 1390:(the result of the 1287:Alzheimer's disease 1060:Parkinson's disease 1056:Alzheimer's disease 793:hyperphosphorylated 781:Alzheimer's disease 485:lower motor neurons 481:upper motor neurons 447:proteolipid protein 398:polyglutamine tract 277:Parkinson's disease 272:Parkinson's disease 266:Parkinson's disease 211:, and parts of the 185:Alzheimer's disease 180:Alzheimer's disease 166:Alzheimer's disease 117:Alzheimer's disease 113:Parkinson's disease 63:Alzheimer's disease 6841:Neuroimmune system 6735:Neurophenomenology 6675:Neural engineering 6398:Neuroendocrinology 6378:Neural engineering 6115:Pseudobulbar palsy 5853:Status epilepticus 5804:Multiple sclerosis 5641:Myoclonic epilepsy 5504:movement disorders 5450:Acute disseminated 5392:Viral encephalitis 5014:10.1007/BF03256900 3537:10.1038/nn0507-535 3322:Muscle & Nerve 3262:Scientific Reports 2934:Journal of Anatomy 2755:Movement Disorders 2535:HHMI Research News 2501:Revue Neurologique 2378:10.1042/BST0330335 1141:Apoptosis (type I) 1107:cytoplasmic dynein 1052:oculomotor apraxia 919:neurodegeneration. 828:main component of 751:misfolded proteins 731:Protein misfolding 696:), and fruit fly ( 631: 427:Multiple sclerosis 422:Multiple sclerosis 416:Multiple sclerosis 383:subthalamic nuclei 352:autosomal dominant 323:glucocerebrosidase 294:, a region of the 176: 158:Specific disorders 109:multiple sclerosis 6911: 6910: 6760:Paleoneurobiology 6695:Neuroepistemology 6670:Neuroanthropology 6636:Interdisciplinary 6522:Neuropharmacology 6482:Neuroepidemiology 6253: 6252: 6249: 6248: 6245: 6244: 6049: 6048: 5954: 5953: 5893:Template:Headache 5859:Template:Epilepsy 5780: 5779: 5754:Vascular dementia 5597:Status dystonicus 5470: 5469: 5445:Encephalomyelitis 5323: 5322: 4743:Annu Rev Neurosci 4594:(Pt A): 163–176. 4016:(7): 1086–93.e2. 3888:978-0-12-092860-6 3751:www.ninds.nih.gov 3575:www.ninds.nih.gov 3334:10.1002/mus.26764 3125:978-0-7234-3748-2 3091:www.ninds.nih.gov 2989:(6505): 787–793. 2815:978-0-87893-742-4 2767:10.1002/mds.26942 2655:: 209.e1–209.e7. 2155:978-1-4008-4846-1 2123:(Suppl 9): 7–10. 2067:978-1-4020-9434-7 2035:978-92-4-003324-5 1975:(7113): 796–802. 1774:10.1111/imm.12922 1640:www.ninds.nih.gov 1346:transglutaminases 1271:Transglutaminase 1236:Transglutaminases 1072:Cockayne syndrome 1048:repair mechanisms 666:genetic mutations 97:neurodegeneration 85: 84: 37:Medical condition 18:Neurodegeneration 16:(Redirected from 6946: 6899: 6898: 6887: 6886: 6801:Detection theory 6685:Neurocriminology 6612:Neurolinguistics 6527:Neuroprosthetics 6445: 6408:Neuroinformatics 6358:Imaging genetics 6280: 6273: 6266: 6257: 6067: 6058: 6016:Brain herniation 5827: 5667:Intention tremor 5662:Essential tremor 5527:Postencephalitic 5495: 5486: 5375: 5356:Diseases of the 5350: 5343: 5336: 5327: 5273: 5266: 5265: 5254: 5248: 5247: 5237: 5227: 5203: 5197: 5196: 5171:(4959): 1122–4. 5160: 5154: 5153: 5117: 5111: 5110: 5100: 5068: 5062: 5061: 5024: 5018: 5017: 4997: 4991: 4986: 4980: 4979: 4943: 4920: 4919: 4909: 4898:10.1172/JCI26321 4877: 4871: 4870: 4834: 4828: 4827: 4817: 4807: 4783: 4777: 4776: 4766: 4734: 4728: 4727: 4717: 4685: 4674: 4673: 4663: 4631: 4622: 4621: 4611: 4579: 4570: 4569: 4559: 4549: 4525: 4519: 4518: 4490: 4484: 4483: 4473: 4463: 4439: 4433: 4432: 4422: 4412: 4387: 4381: 4380: 4370: 4360: 4336: 4330: 4329: 4319: 4309: 4285: 4279: 4278: 4268: 4258: 4234: 4223: 4222: 4204: 4172: 4163: 4162: 4152: 4142: 4118: 4112: 4109: 4107: 4105: 4055: 4045: 4035: 4025: 4000: 3991: 3990: 3980: 3957:The EMBO Journal 3948: 3942: 3941: 3931: 3899: 3893: 3892: 3874: 3868: 3867: 3834:(7113): 787–95. 3823: 3814: 3813: 3811: 3809: 3794: 3788: 3787: 3785: 3783: 3769: 3763: 3762: 3760: 3758: 3743: 3737: 3736: 3708: 3702: 3701: 3691: 3659: 3646: 3645: 3635: 3603: 3586: 3585: 3583: 3581: 3567: 3558: 3557: 3539: 3515: 3509: 3508: 3498: 3458: 3452: 3451: 3441: 3409: 3403: 3402: 3392: 3360: 3354: 3353: 3317: 3304: 3303: 3293: 3253: 3242: 3241: 3231: 3221: 3197: 3191: 3190: 3180: 3170: 3146: 3135: 3134: 3133: 3132: 3107: 3101: 3100: 3098: 3097: 3083: 3074: 3073: 3063: 3031: 3025: 3024: 3014: 2973: 2964: 2963: 2953: 2925: 2919: 2910: 2904: 2903: 2893: 2861: 2855: 2854: 2826: 2820: 2819: 2795: 2789: 2788: 2778: 2745: 2739: 2738: 2728: 2718: 2694: 2683: 2682: 2672: 2640: 2634: 2633: 2623: 2613: 2604:(42): 32486–93. 2589: 2578: 2577: 2549: 2538: 2531: 2525: 2524: 2496: 2490: 2489: 2471: 2439: 2433: 2432: 2396: 2390: 2389: 2361: 2355: 2354: 2318: 2312: 2311: 2301: 2269: 2263: 2262: 2252: 2228: 2219: 2218: 2208: 2198: 2174: 2168: 2167: 2139: 2133: 2132: 2112: 2106: 2105: 2078: 2072: 2071: 2053: 2047: 2046: 2044: 2042: 2027: 2017: 2011: 2010: 2000: 1960: 1941: 1940: 1896: 1873: 1872: 1870: 1868: 1853: 1847: 1846: 1836: 1826: 1802: 1796: 1795: 1785: 1753: 1747: 1746: 1736: 1726: 1702: 1696: 1695: 1685: 1657: 1651: 1650: 1648: 1646: 1632: 1626: 1625: 1615: 1605: 1581: 1575: 1574: 1564: 1530: 1406:isopeptide bonds 1402:Co-localization: 1392:transglutaminase 1388:isopeptide bonds 1386:The presence of 1382:isopeptide bonds 1371:transglutaminase 1361:Transglutaminase 1318:Transglutaminase 1258:isopeptide bonds 1231:Transglutaminase 1099:Axonal transport 1094:axonal spheroids 1088:Axonal transport 1082:Axonal transport 1011:oxidative damage 970:oxidative stress 609:oxidative stress 406:axonal transport 402:inclusion bodies 396:HD is caused by 292:substantia nigra 52: 40: 21: 6954: 6953: 6949: 6948: 6947: 6945: 6944: 6943: 6914: 6913: 6912: 6907: 6875: 6861:Neurotechnology 6856:Neuroplasticity 6851:Neuromodulation 6846:Neuromanagement 6769: 6740:Neurophilosophy 6637: 6631: 6617:Neuropsychology 6578: 6571: 6532:Neuropsychiatry 6492:Neuroimmunology 6477:Neurocardiology 6453: 6446: 6437: 6428:Neurophysiology 6418:Neuromorphology 6373:Neural decoding 6314: 6307: 6289: 6284: 6254: 6241: 6167:Congenital DSMA 6088: 6045: 6004: 5950: 5938:Sleep disorders 5926: 5903:Cerebrovascular 5897: 5863: 5820: 5814: 5776: 5758: 5683: 5629:Choreoathetosis 5502: 5479: 5466: 5430: 5364: 5354: 5324: 5319: 5318: 5284: 5270: 5269: 5256: 5255: 5251: 5205: 5204: 5200: 5162: 5161: 5157: 5119: 5118: 5114: 5070: 5069: 5065: 5026: 5025: 5021: 4999: 4998: 4994: 4987: 4983: 4945: 4944: 4923: 4879: 4878: 4874: 4851:10.1038/nrn1100 4836: 4835: 4831: 4785: 4784: 4780: 4736: 4735: 4731: 4687: 4686: 4677: 4633: 4632: 4625: 4581: 4580: 4573: 4527: 4526: 4522: 4492: 4491: 4487: 4454:(17): 3159–80. 4441: 4440: 4436: 4389: 4388: 4384: 4338: 4337: 4333: 4287: 4286: 4282: 4236: 4235: 4226: 4202:10.1038/452707a 4187:(7188): 707–8. 4174: 4173: 4166: 4133:(8): e1010670. 4120: 4119: 4115: 4103: 4101: 4064:(7946): 18–19. 4049: 4002: 4001: 3994: 3963:(11): 1474–92. 3950: 3949: 3945: 3914:(10): a025130. 3901: 3900: 3896: 3889: 3876: 3875: 3871: 3825: 3824: 3817: 3807: 3805: 3796: 3795: 3791: 3781: 3779: 3771: 3770: 3766: 3756: 3754: 3745: 3744: 3740: 3710: 3709: 3705: 3661: 3660: 3649: 3605: 3604: 3589: 3579: 3577: 3569: 3568: 3561: 3517: 3516: 3512: 3460: 3459: 3455: 3411: 3410: 3406: 3362: 3361: 3357: 3319: 3318: 3307: 3255: 3254: 3245: 3219:10.1.1.328.2931 3199: 3198: 3194: 3148: 3147: 3138: 3130: 3128: 3126: 3109: 3108: 3104: 3095: 3093: 3085: 3084: 3077: 3033: 3032: 3028: 2975: 2974: 2967: 2927: 2926: 2922: 2911: 2907: 2876:(11): 1355–60. 2863: 2862: 2858: 2828: 2827: 2823: 2816: 2797: 2796: 2792: 2747: 2746: 2742: 2696: 2695: 2686: 2642: 2641: 2637: 2591: 2590: 2581: 2551: 2550: 2541: 2532: 2528: 2498: 2497: 2493: 2441: 2440: 2436: 2398: 2397: 2393: 2372:(Pt 2): 335–8. 2363: 2362: 2358: 2320: 2319: 2315: 2284:(27): 7212–21. 2271: 2270: 2266: 2230: 2229: 2222: 2176: 2175: 2171: 2156: 2141: 2140: 2136: 2114: 2113: 2109: 2080: 2079: 2075: 2068: 2055: 2054: 2050: 2040: 2038: 2036: 2025: 2019: 2018: 2014: 1962: 1961: 1944: 1907:(7113): 780–6. 1898: 1897: 1876: 1866: 1864: 1855: 1854: 1850: 1804: 1803: 1799: 1755: 1754: 1750: 1704: 1703: 1699: 1659: 1658: 1654: 1644: 1642: 1634: 1633: 1629: 1583: 1582: 1578: 1532: 1531: 1524: 1519: 1492: 1456: 1430:palliative care 1426: 1418: 1334:alpha-synuclein 1309:disease, it is 1303:alpha-synuclein 1301:disease, it is 1233: 1219: 1203: 1176:Golgi apparatus 1143: 1127: 1113:, cargoes, and 1090: 1084: 1027: 950: 935: 933:Membrane damage 848: 843: 777:amyloid plaques 759:alpha-synuclein 739: 733: 717: 662: 652: 647: 623: 597: 591: 586: 563: 557: 530: 524: 470: 464: 424: 418: 387:globus pallidus 356:huntingtin gene 350:(HD) is a rare 345: 339: 300:alpha-synuclein 290:neurons in the 274: 268: 256:gamma secretase 224:amyloid plaques 217:cingulate gyrus 197:cerebral cortex 182: 168: 160: 38: 35: 28: 23: 22: 15: 12: 11: 5: 6952: 6950: 6942: 6941: 6936: 6931: 6926: 6916: 6915: 6909: 6908: 6906: 6905: 6893: 6880: 6877: 6876: 6874: 6873: 6871:Self-awareness 6868: 6863: 6858: 6853: 6848: 6843: 6838: 6833: 6828: 6826:Neurodiversity 6823: 6818: 6813: 6808: 6803: 6798: 6793: 6788: 6783: 6777: 6775: 6771: 6770: 6768: 6767: 6762: 6757: 6752: 6747: 6742: 6737: 6732: 6727: 6725:Neuromarketing 6722: 6717: 6712: 6707: 6702: 6700:Neuroesthetics 6697: 6692: 6690:Neuroeconomics 6687: 6682: 6677: 6672: 6667: 6662: 6657: 6652: 6647: 6641: 6639: 6633: 6632: 6630: 6629: 6624: 6619: 6614: 6609: 6604: 6599: 6594: 6589: 6583: 6581: 6573: 6572: 6570: 6569: 6564: 6559: 6554: 6549: 6544: 6539: 6537:Neuroradiology 6534: 6529: 6524: 6519: 6517:Neuropathology 6514: 6509: 6507:Neuro-oncology 6504: 6499: 6494: 6489: 6484: 6479: 6474: 6469: 6464: 6458: 6456: 6448: 6447: 6440: 6438: 6436: 6435: 6430: 6425: 6420: 6415: 6410: 6405: 6400: 6395: 6393:Neurochemistry 6390: 6385: 6380: 6375: 6370: 6365: 6360: 6355: 6350: 6345: 6340: 6335: 6330: 6325: 6319: 6317: 6309: 6308: 6306: 6305: 6300: 6294: 6291: 6290: 6285: 6283: 6282: 6275: 6268: 6260: 6251: 6250: 6247: 6246: 6243: 6242: 6240: 6239: 6238: 6237: 6226: 6225: 6224: 6223: 6222: 6221: 6216: 6206: 6201: 6200: 6199: 6194: 6189: 6188: 6187: 6182: 6177: 6169: 6164: 6159: 6154: 6149: 6139: 6125: 6124: 6123: 6122: 6117: 6112: 6098: 6096: 6090: 6089: 6087: 6086: 6081: 6075: 6073: 6064: 6055: 6051: 6050: 6047: 6046: 6044: 6043: 6038: 6033: 6028: 6023: 6018: 6012: 6010: 6006: 6005: 6003: 6002: 5997: 5995:Cerebral edema 5992: 5991: 5990: 5985: 5980: 5975: 5964: 5962: 5956: 5955: 5952: 5951: 5949: 5948: 5947: 5946: 5944:Template:Sleep 5934: 5932: 5928: 5927: 5925: 5924: 5918: 5913: 5907: 5905: 5899: 5898: 5896: 5895: 5889: 5884: 5879: 5873: 5871: 5865: 5864: 5862: 5861: 5855: 5850: 5845: 5839: 5837: 5824: 5816: 5815: 5813: 5812: 5806: 5801: 5796: 5790: 5788: 5782: 5781: 5778: 5777: 5775: 5774: 5772:Leigh syndrome 5768: 5766: 5760: 5759: 5757: 5756: 5745: 5744: 5739: 5734: 5733: 5732: 5718: 5717: 5716: 5711: 5710: 5709: 5693: 5691: 5685: 5684: 5682: 5681: 5676: 5671: 5670: 5669: 5664: 5653: 5652: 5651: 5650: 5645: 5644: 5643: 5633: 5632: 5631: 5621: 5616: 5615: 5614: 5609: 5604: 5599: 5583: 5582: 5581: 5580: 5575: 5570: 5565: 5560: 5559: 5558: 5548: 5547: 5546: 5536: 5535: 5534: 5529: 5524: 5508: 5506: 5499:Extrapyramidal 5492: 5483: 5481:encephalopathy 5472: 5471: 5468: 5467: 5465: 5464: 5459: 5454: 5453: 5452: 5441: 5439: 5432: 5431: 5429: 5428: 5427: 5426: 5416: 5411: 5410: 5409: 5404: 5399: 5394: 5383: 5381: 5372: 5366: 5365: 5358:nervous system 5355: 5353: 5352: 5345: 5338: 5330: 5321: 5320: 5317: 5316: 5305: 5285: 5280: 5279: 5277: 5276:Classification 5268: 5267: 5249: 5218:(9): a006387. 5198: 5155: 5112: 5063: 5019: 4992: 4981: 4921: 4892:(10): 2610–7. 4872: 4829: 4778: 4729: 4700:(2): 166–200. 4675: 4646:(2): 266–282. 4623: 4571: 4520: 4485: 4434: 4397:Genome Biology 4382: 4351:(12): 7425–9. 4331: 4280: 4249:(12): 7431–5. 4224: 4164: 4127:PLOS Pathogens 4113: 4111: 4110: 3992: 3943: 3894: 3887: 3869: 3815: 3789: 3764: 3738: 3703: 3647: 3618:(3): 161–178. 3587: 3559: 3510: 3473:(6): a020628. 3453: 3430:10.1038/nn1885 3404: 3381:10.1038/nn1876 3355: 3328:(4): 508–511. 3305: 3243: 3212:(6): 1464–77. 3192: 3136: 3124: 3102: 3075: 3026: 2965: 2920: 2905: 2882:10.1038/nn1988 2856: 2821: 2814: 2790: 2761:(5): 739–749. 2740: 2684: 2635: 2579: 2539: 2537:June 22, 2006. 2526: 2491: 2454:(5): 511–524. 2434: 2407:(11): 1984–9. 2391: 2356: 2313: 2264: 2220: 2169: 2154: 2134: 2107: 2073: 2066: 2048: 2034: 2012: 1942: 1874: 1863:. 17 July 2014 1848: 1797: 1768:(2): 204–219. 1748: 1697: 1652: 1627: 1576: 1521: 1520: 1518: 1515: 1514: 1513: 1508: 1503: 1498: 1491: 1488: 1455: 1452: 1425: 1422: 1417: 1414: 1376:is increased. 1354:covalent bonds 1262:transamidation 1254:covalent bonds 1232: 1229: 1218: 1215: 1202: 1199: 1180: 1179: 1161: 1142: 1139: 1126: 1123: 1086:Main article: 1083: 1080: 1026: 1023: 949: 946: 934: 931: 930: 929: 928: 927: 920: 916:macroautophagy 905:macroautophagy 893: 892: 891: 873: 872: 869: 866: 861:nucleus, e.g. 859: 847: 844: 842: 839: 838: 837: 830:prion diseases 820: 811: 784: 737:Stress granule 732: 729: 716: 713: 651: 648: 646: 643: 633:A study using 622: 619: 590: 587: 585: 582: 559:Main article: 556: 553: 533:Batten disease 528:Batten disease 526:Main article: 523: 522:Batten disease 520: 466:Main article: 463: 460: 456:HLA-DRB1*15:01 420:Main article: 417: 414: 341:Main article: 338: 335: 331:gut microbiome 270:Main article: 267: 264: 260:beta secretase 213:frontal cortex 178:Main article: 167: 164: 159: 156: 133:prion diseases 83: 82: 73: 67: 66: 54: 53: 45: 44: 36: 26: 24: 14: 13: 10: 9: 6: 4: 3: 2: 6951: 6940: 6937: 6935: 6932: 6930: 6927: 6925: 6922: 6921: 6919: 6904: 6903: 6894: 6892: 6891: 6882: 6881: 6878: 6872: 6869: 6867: 6864: 6862: 6859: 6857: 6854: 6852: 6849: 6847: 6844: 6842: 6839: 6837: 6834: 6832: 6829: 6827: 6824: 6822: 6819: 6817: 6814: 6812: 6809: 6807: 6804: 6802: 6799: 6797: 6794: 6792: 6789: 6787: 6784: 6782: 6779: 6778: 6776: 6772: 6766: 6763: 6761: 6758: 6756: 6755:Neurotheology 6753: 6751: 6750:Neurorobotics 6748: 6746: 6745:Neuropolitics 6743: 6741: 6738: 6736: 6733: 6731: 6728: 6726: 6723: 6721: 6718: 6716: 6713: 6711: 6710:Neuroethology 6708: 6706: 6703: 6701: 6698: 6696: 6693: 6691: 6688: 6686: 6683: 6681: 6678: 6676: 6673: 6671: 6668: 6666: 6663: 6661: 6658: 6656: 6653: 6651: 6648: 6646: 6643: 6642: 6640: 6634: 6628: 6625: 6623: 6620: 6618: 6615: 6613: 6610: 6608: 6607:Motor control 6605: 6603: 6600: 6598: 6597:Chronobiology 6595: 6593: 6590: 6588: 6585: 6584: 6582: 6580: 6574: 6568: 6565: 6563: 6560: 6558: 6557:Neurovirology 6555: 6553: 6550: 6548: 6545: 6543: 6540: 6538: 6535: 6533: 6530: 6528: 6525: 6523: 6520: 6518: 6515: 6513: 6510: 6508: 6505: 6503: 6500: 6498: 6495: 6493: 6490: 6488: 6485: 6483: 6480: 6478: 6475: 6473: 6470: 6468: 6465: 6463: 6460: 6459: 6457: 6455: 6449: 6444: 6434: 6431: 6429: 6426: 6424: 6421: 6419: 6416: 6414: 6411: 6409: 6406: 6404: 6403:Neurogenetics 6401: 6399: 6396: 6394: 6391: 6389: 6386: 6384: 6381: 6379: 6376: 6374: 6371: 6369: 6366: 6364: 6361: 6359: 6356: 6354: 6351: 6349: 6346: 6344: 6341: 6339: 6338:Brain-reading 6336: 6334: 6333:Brain mapping 6331: 6329: 6326: 6324: 6321: 6320: 6318: 6316: 6310: 6304: 6301: 6299: 6296: 6295: 6292: 6288: 6281: 6276: 6274: 6269: 6267: 6262: 6261: 6258: 6236: 6233: 6232: 6231: 6228: 6227: 6220: 6217: 6215: 6212: 6211: 6210: 6207: 6205: 6202: 6198: 6195: 6193: 6190: 6186: 6183: 6181: 6178: 6176: 6173: 6172: 6170: 6168: 6165: 6163: 6160: 6158: 6155: 6153: 6150: 6148: 6145: 6144: 6143: 6140: 6138: 6135: 6134: 6133: 6131: 6127: 6126: 6121: 6118: 6116: 6113: 6111: 6108: 6107: 6106: 6104: 6100: 6099: 6097: 6095: 6091: 6085: 6082: 6080: 6077: 6076: 6074: 6072: 6068: 6065: 6063: 6059: 6056: 6052: 6042: 6039: 6037: 6034: 6032: 6029: 6027: 6024: 6022: 6021:Reye syndrome 6019: 6017: 6014: 6013: 6011: 6007: 6001: 5998: 5996: 5993: 5989: 5986: 5984: 5981: 5979: 5976: 5974: 5973:Hydrocephalus 5971: 5970: 5969: 5966: 5965: 5963: 5961: 5957: 5945: 5941: 5940: 5939: 5936: 5935: 5933: 5929: 5923: 5919: 5917: 5914: 5912: 5909: 5908: 5906: 5904: 5900: 5894: 5890: 5888: 5885: 5883: 5880: 5878: 5875: 5874: 5872: 5870: 5866: 5860: 5856: 5854: 5851: 5849: 5846: 5844: 5841: 5840: 5838: 5836: 5832: 5828: 5825: 5823: 5817: 5811: 5807: 5805: 5802: 5800: 5797: 5795: 5792: 5791: 5789: 5787: 5786:Demyelinating 5783: 5773: 5770: 5769: 5767: 5765: 5761: 5755: 5752: 5751: 5750: 5749: 5743: 5740: 5738: 5735: 5731: 5728: 5727: 5726: 5722: 5719: 5715: 5712: 5708: 5705: 5704: 5703: 5700: 5699: 5698: 5695: 5694: 5692: 5690: 5686: 5680: 5677: 5675: 5674:Restless legs 5672: 5668: 5665: 5663: 5660: 5659: 5658: 5655: 5654: 5649: 5646: 5642: 5639: 5638: 5637: 5634: 5630: 5627: 5626: 5625: 5622: 5620: 5617: 5613: 5612:Blepharospasm 5610: 5608: 5605: 5603: 5600: 5598: 5595: 5594: 5593: 5590: 5589: 5588: 5585: 5584: 5579: 5576: 5574: 5571: 5569: 5568:Hemiballismus 5566: 5564: 5561: 5557: 5554: 5553: 5552: 5549: 5545: 5542: 5541: 5540: 5537: 5533: 5530: 5528: 5525: 5523: 5520: 5519: 5518: 5515: 5514: 5513: 5510: 5509: 5507: 5505: 5500: 5496: 5493: 5491: 5487: 5484: 5482: 5477: 5473: 5463: 5460: 5458: 5455: 5451: 5448: 5447: 5446: 5443: 5442: 5440: 5438: 5433: 5425: 5422: 5421: 5420: 5419:Brain abscess 5417: 5415: 5412: 5408: 5405: 5403: 5400: 5398: 5395: 5393: 5390: 5389: 5388: 5385: 5384: 5382: 5380: 5376: 5373: 5371: 5367: 5363: 5359: 5351: 5346: 5344: 5339: 5337: 5332: 5331: 5328: 5315: 5311: 5310: 5306: 5304: 5300: 5296: 5295: 5291: 5287: 5286: 5283: 5278: 5274: 5263: 5259: 5253: 5250: 5245: 5241: 5236: 5231: 5226: 5221: 5217: 5213: 5209: 5202: 5199: 5194: 5190: 5186: 5182: 5178: 5174: 5170: 5166: 5159: 5156: 5151: 5147: 5143: 5139: 5135: 5131: 5127: 5123: 5116: 5113: 5108: 5104: 5099: 5094: 5090: 5086: 5082: 5078: 5074: 5067: 5064: 5059: 5055: 5051: 5047: 5043: 5039: 5036:(5): 332–44. 5035: 5031: 5023: 5020: 5015: 5011: 5007: 5003: 4996: 4993: 4990: 4985: 4982: 4977: 4973: 4969: 4965: 4961: 4957: 4953: 4949: 4942: 4940: 4938: 4936: 4934: 4932: 4930: 4928: 4926: 4922: 4917: 4913: 4908: 4903: 4899: 4895: 4891: 4887: 4883: 4876: 4873: 4868: 4864: 4860: 4856: 4852: 4848: 4845:(5): 365–75. 4844: 4840: 4833: 4830: 4825: 4821: 4816: 4811: 4806: 4801: 4797: 4793: 4792:PLOS Genetics 4789: 4782: 4779: 4774: 4770: 4765: 4760: 4756: 4752: 4748: 4744: 4740: 4733: 4730: 4725: 4721: 4716: 4711: 4707: 4703: 4699: 4695: 4691: 4684: 4682: 4680: 4676: 4671: 4667: 4662: 4657: 4653: 4649: 4645: 4641: 4637: 4630: 4628: 4624: 4619: 4615: 4610: 4605: 4601: 4597: 4593: 4589: 4585: 4578: 4576: 4572: 4567: 4563: 4558: 4553: 4548: 4543: 4539: 4535: 4531: 4524: 4521: 4516: 4512: 4508: 4504: 4500: 4496: 4489: 4486: 4481: 4477: 4472: 4467: 4462: 4457: 4453: 4449: 4445: 4438: 4435: 4430: 4426: 4421: 4416: 4411: 4406: 4402: 4398: 4394: 4386: 4383: 4378: 4374: 4369: 4364: 4359: 4354: 4350: 4346: 4342: 4335: 4332: 4327: 4323: 4318: 4313: 4308: 4303: 4299: 4295: 4291: 4284: 4281: 4276: 4272: 4267: 4262: 4257: 4252: 4248: 4244: 4240: 4233: 4231: 4229: 4225: 4220: 4216: 4212: 4208: 4203: 4198: 4194: 4190: 4186: 4182: 4178: 4171: 4169: 4165: 4160: 4156: 4151: 4146: 4141: 4136: 4132: 4128: 4124: 4117: 4114: 4099: 4095: 4091: 4087: 4083: 4079: 4075: 4071: 4067: 4063: 4059: 4054: 4047: 4046: 4043: 4039: 4034: 4029: 4024: 4019: 4015: 4011: 4007: 3999: 3997: 3993: 3988: 3984: 3979: 3974: 3970: 3966: 3962: 3958: 3954: 3947: 3944: 3939: 3935: 3930: 3925: 3921: 3917: 3913: 3909: 3905: 3898: 3895: 3890: 3884: 3880: 3873: 3870: 3865: 3861: 3857: 3853: 3849: 3845: 3841: 3837: 3833: 3829: 3822: 3820: 3816: 3804: 3800: 3793: 3790: 3778: 3774: 3768: 3765: 3752: 3748: 3742: 3739: 3734: 3730: 3726: 3722: 3718: 3714: 3707: 3704: 3699: 3695: 3690: 3685: 3681: 3677: 3673: 3669: 3665: 3658: 3656: 3654: 3652: 3648: 3643: 3639: 3634: 3629: 3625: 3621: 3617: 3613: 3609: 3602: 3600: 3598: 3596: 3594: 3592: 3588: 3576: 3572: 3566: 3564: 3560: 3555: 3551: 3547: 3543: 3538: 3533: 3529: 3525: 3521: 3514: 3511: 3506: 3502: 3497: 3492: 3488: 3484: 3480: 3476: 3472: 3468: 3464: 3457: 3454: 3449: 3445: 3440: 3435: 3431: 3427: 3424:(5): 608–14. 3423: 3419: 3415: 3408: 3405: 3400: 3396: 3391: 3386: 3382: 3378: 3375:(5): 615–22. 3374: 3370: 3366: 3359: 3356: 3351: 3347: 3343: 3339: 3335: 3331: 3327: 3323: 3316: 3314: 3312: 3310: 3306: 3301: 3297: 3292: 3287: 3283: 3279: 3275: 3271: 3267: 3263: 3259: 3252: 3250: 3248: 3244: 3239: 3235: 3230: 3225: 3220: 3215: 3211: 3207: 3203: 3196: 3193: 3188: 3184: 3179: 3174: 3169: 3164: 3160: 3156: 3155:F1000Research 3152: 3145: 3143: 3141: 3137: 3127: 3121: 3117: 3113: 3106: 3103: 3092: 3088: 3082: 3080: 3076: 3071: 3067: 3062: 3057: 3053: 3049: 3046:(8): 378–85. 3045: 3041: 3037: 3030: 3027: 3022: 3018: 3013: 3008: 3004: 3000: 2996: 2992: 2988: 2984: 2980: 2972: 2970: 2966: 2961: 2957: 2952: 2947: 2943: 2939: 2935: 2931: 2924: 2921: 2918: 2914: 2909: 2906: 2901: 2897: 2892: 2887: 2883: 2879: 2875: 2871: 2867: 2860: 2857: 2852: 2848: 2844: 2840: 2837:(3): 265–76. 2836: 2832: 2825: 2822: 2817: 2811: 2807: 2806: 2801: 2794: 2791: 2786: 2782: 2777: 2772: 2768: 2764: 2760: 2756: 2752: 2744: 2741: 2736: 2732: 2727: 2722: 2717: 2712: 2708: 2704: 2700: 2693: 2691: 2689: 2685: 2680: 2676: 2671: 2666: 2662: 2658: 2654: 2650: 2646: 2639: 2636: 2631: 2627: 2622: 2617: 2612: 2607: 2603: 2599: 2595: 2588: 2586: 2584: 2580: 2575: 2571: 2567: 2563: 2559: 2555: 2548: 2546: 2544: 2540: 2536: 2530: 2527: 2522: 2518: 2514: 2510: 2506: 2502: 2495: 2492: 2487: 2483: 2479: 2475: 2470: 2465: 2461: 2457: 2453: 2449: 2445: 2438: 2435: 2430: 2426: 2422: 2418: 2414: 2410: 2406: 2402: 2395: 2392: 2387: 2383: 2379: 2375: 2371: 2367: 2360: 2357: 2352: 2348: 2344: 2340: 2336: 2332: 2328: 2324: 2317: 2314: 2309: 2305: 2300: 2295: 2291: 2287: 2283: 2279: 2275: 2268: 2265: 2260: 2256: 2251: 2246: 2242: 2238: 2234: 2227: 2225: 2221: 2216: 2212: 2207: 2202: 2197: 2192: 2188: 2184: 2180: 2173: 2170: 2165: 2161: 2157: 2151: 2147: 2146: 2138: 2135: 2130: 2126: 2122: 2118: 2111: 2108: 2103: 2099: 2095: 2091: 2087: 2083: 2077: 2074: 2069: 2063: 2059: 2052: 2049: 2037: 2031: 2024: 2023: 2016: 2013: 2008: 2004: 1999: 1994: 1990: 1986: 1982: 1978: 1974: 1970: 1966: 1959: 1957: 1955: 1953: 1951: 1949: 1947: 1943: 1938: 1934: 1930: 1926: 1922: 1918: 1914: 1910: 1906: 1902: 1895: 1893: 1891: 1889: 1887: 1885: 1883: 1881: 1879: 1875: 1862: 1861:JPND Research 1858: 1852: 1849: 1844: 1840: 1835: 1830: 1825: 1820: 1816: 1812: 1808: 1801: 1798: 1793: 1789: 1784: 1779: 1775: 1771: 1767: 1763: 1759: 1752: 1749: 1744: 1740: 1735: 1730: 1725: 1720: 1716: 1712: 1708: 1701: 1698: 1693: 1689: 1684: 1679: 1675: 1671: 1667: 1663: 1656: 1653: 1641: 1637: 1631: 1628: 1623: 1619: 1614: 1609: 1604: 1599: 1595: 1591: 1590:Int J Mol Sci 1587: 1580: 1577: 1572: 1568: 1563: 1558: 1554: 1550: 1546: 1542: 1541: 1536: 1529: 1527: 1523: 1516: 1512: 1509: 1507: 1504: 1502: 1501:JUNQ and IPOD 1499: 1497: 1494: 1493: 1489: 1487: 1485: 1481: 1477: 1472: 1468: 1465: 1464:immunotherapy 1460: 1453: 1451: 1449: 1443: 1440: 1435: 1434:animal models 1431: 1423: 1421: 1415: 1413: 1411: 1407: 1403: 1399: 1397: 1393: 1389: 1385: 1383: 1377: 1375: 1372: 1368: 1364: 1362: 1357: 1355: 1351: 1347: 1343: 1339: 1335: 1331: 1327: 1324: 1322: 1319: 1314: 1312: 1308: 1304: 1300: 1296: 1292: 1288: 1283: 1281: 1276: 1274: 1269: 1267: 1263: 1259: 1255: 1251: 1246: 1244: 1241: 1237: 1230: 1228: 1225: 1216: 1214: 1212: 1211:autophagosome 1208: 1200: 1198: 1196: 1192: 1188: 1184: 1177: 1173: 1169: 1165: 1162: 1159: 1155: 1152: 1151: 1150: 1147: 1140: 1138: 1135: 1131: 1124: 1122: 1120: 1116: 1112: 1108: 1104: 1100: 1095: 1089: 1081: 1079: 1077: 1073: 1069: 1065: 1061: 1057: 1053: 1049: 1044: 1040: 1036: 1032: 1024: 1022: 1020: 1016: 1015:transcription 1012: 1008: 1004: 1002: 998: 994: 990: 985: 983: 979: 975: 971: 967: 963: 959: 955: 947: 945: 944: 941: 932: 924: 921: 917: 914: 913: 911: 907: 906: 901: 897: 894: 889: 888: 885: 881: 878: 877: 876: 870: 867: 864: 860: 857: 856: 855: 853: 852:proteopathies 845: 840: 835: 831: 827: 825: 821: 818: 816: 812: 809: 805: 801: 797: 794: 791: 789: 785: 782: 778: 774: 770: 766: 762: 760: 756: 755: 754: 752: 748: 744: 743:proteopathies 738: 730: 728: 726: 725:Braak staging 722: 714: 712: 710: 706: 701: 699: 695: 691: 687: 681: 679: 675: 671: 667: 661: 657: 649: 644: 642: 640: 636: 627: 620: 618: 615: 610: 606: 602: 596: 588: 583: 581: 579: 575: 571: 567: 562: 554: 552: 550: 546: 542: 538: 534: 529: 521: 519: 517: 516:motor neurons 513: 509: 504: 502: 498: 494: 490: 486: 482: 478: 474: 469: 461: 459: 457: 452: 448: 444: 440: 436: 432: 428: 423: 415: 413: 411: 407: 403: 399: 394: 392: 388: 384: 380: 376: 372: 368: 364: 360: 357: 353: 349: 344: 334: 332: 328: 324: 320: 315: 313: 309: 305: 301: 297: 293: 289: 284: 282: 278: 273: 263: 261: 257: 253: 249: 245: 241: 237: 233: 229: 225: 220: 218: 214: 210: 209:parietal lobe 206: 205:temporal lobe 202: 198: 194: 190: 186: 181: 172: 163: 157: 155: 153: 148: 146: 142: 141:proteinopathy 138: 134: 130: 126: 122: 118: 114: 110: 106: 102: 98: 94: 90: 81: 77: 74: 72: 68: 64: 60: 55: 51: 46: 41: 33: 19: 6900: 6888: 6836:Neuroimaging 6831:Neurogenesis 6815: 6715:Neurohistory 6680:Neurobiotics 6579:neuroscience 6547:Neurosurgery 6472:Epileptology 6454:neuroscience 6423:Neurophysics 6413:Neurometrics 6388:Neurobiology 6383:Neuroanatomy 6353:Connectomics 6287:Neuroscience 6229: 6128: 6101: 6062:Degenerative 6061: 5799:Inflammatory 5746: 5679:Stiff-person 5517:Parkinsonism 5490:Degenerative 5489: 5387:Encephalitis 5370:Inflammation 5360:, primarily 5307: 5288: 5252: 5215: 5211: 5201: 5168: 5164: 5158: 5128:(4): 642–9. 5125: 5121: 5115: 5080: 5076: 5066: 5033: 5029: 5022: 5008:(2): 113–5. 5005: 5001: 4995: 4984: 4954:(2): 653–8. 4951: 4947: 4889: 4885: 4875: 4842: 4838: 4832: 4798:(10): e135. 4795: 4791: 4781: 4746: 4742: 4732: 4697: 4693: 4643: 4639: 4591: 4587: 4537: 4533: 4523: 4498: 4494: 4488: 4451: 4447: 4437: 4400: 4396: 4385: 4348: 4344: 4334: 4300:(12): 7405. 4297: 4293: 4283: 4246: 4242: 4184: 4180: 4130: 4126: 4116: 4102:. Retrieved 4061: 4057: 4013: 4009: 3960: 3956: 3946: 3911: 3907: 3897: 3878: 3872: 3831: 3827: 3806:. Retrieved 3802: 3792: 3780:. Retrieved 3776: 3767: 3755:. Retrieved 3750: 3741: 3716: 3712: 3706: 3671: 3667: 3615: 3611: 3578:. Retrieved 3574: 3530:(5): 535–7. 3527: 3523: 3513: 3470: 3466: 3456: 3421: 3417: 3407: 3372: 3368: 3358: 3325: 3321: 3268:(1): 15661. 3265: 3261: 3209: 3205: 3195: 3158: 3154: 3129:, retrieved 3115: 3105: 3094:. Retrieved 3090: 3043: 3039: 3029: 2986: 2982: 2933: 2923: 2908: 2873: 2869: 2859: 2834: 2830: 2824: 2805:Neuroscience 2804: 2793: 2758: 2754: 2743: 2706: 2702: 2652: 2648: 2638: 2601: 2597: 2557: 2553: 2529: 2507:(1): 14–26. 2504: 2500: 2494: 2451: 2447: 2437: 2404: 2400: 2394: 2369: 2365: 2359: 2326: 2322: 2316: 2281: 2277: 2267: 2240: 2236: 2186: 2182: 2172: 2144: 2137: 2120: 2116: 2110: 2088:. Springer. 2085: 2076: 2057: 2051: 2039:. Retrieved 2021: 2015: 1972: 1968: 1904: 1900: 1865:. Retrieved 1860: 1851: 1814: 1810: 1800: 1765: 1761: 1751: 1717:(11): 1845. 1714: 1711:Antioxidants 1710: 1700: 1665: 1655: 1643:. Retrieved 1639: 1630: 1593: 1589: 1579: 1544: 1538: 1480:table tennis 1473: 1469: 1462:The goal of 1461: 1457: 1448:amyloid-beta 1444: 1427: 1419: 1401: 1400: 1380:Presence of 1379: 1378: 1359: 1358: 1326:Amyloid-beta 1316: 1315: 1307:Huntington's 1291:amyloid-beta 1289:, these are 1284: 1277: 1270: 1266:crosslinking 1247: 1243:ubiquitously 1234: 1220: 1207:phagocytosis 1204: 1194: 1190: 1181: 1168:cytochrome c 1163: 1153: 1144: 1128: 1115:mitochondria 1111:microtubules 1091: 1028: 1005: 997:Huntington's 986: 954:cytochrome c 951: 936: 922: 915: 909: 903: 895: 879: 874: 849: 822: 815:amyloid beta 813: 786: 757: 740: 718: 702: 697: 693: 682: 663: 632: 598: 584:Risk factors 564: 531: 507: 505: 477:Lou Gehrig's 471: 455: 425: 395: 367:astrogliosis 358: 346: 316: 288:dopaminergic 285: 281:bradykinesia 275: 236:amyloid beta 221: 183: 161: 149: 96: 88: 86: 6705:Neuroethics 6552:Neurotology 6214:Fazio–Londe 6054:Both/either 5848:Generalised 5707:Early-onset 5702:Alzheimer's 5437:spinal cord 4948:Amino Acids 4540:: 2525967. 4104:15 February 3777:Mayo Clinic 3580:30 November 2913:Purves 2001 2818:. NBK10847. 2329:(1): 1–32. 2189:: 631–653. 1867:February 7, 1817:(8): 1583. 1596:(3): 1851. 1408:with these 1299:Parkinson's 1019:antioxidant 993:Parkinson's 989:Alzheimer's 926:substrates. 804:Pick bodies 796:tau protein 765:Lewy bodies 747:aggregation 715:Epigenetics 607:as well as 595:Aging brain 568:(CJD) is a 483:(UMNs) and 451:macrophages 327:tau protein 325:(GBA), and 308:Lewy bodies 145:therapeutic 137:subcellular 129:tauopathies 6934:Senescence 6918:Categories 6866:Neurotoxin 6567:Psychiatry 5822:paroxysmal 5794:Autoimmune 5587:Dyskinesia 5457:Meningitis 5435:Brain and 5083:: 175–93. 4749:: 245–67. 4501:: 91–123. 3131:2020-12-07 3096:2020-11-30 2560:: 151–73. 2041:14 October 1762:Immunology 1517:References 1416:Management 1367:expression 1342:substrates 1338:huntingtin 1321:substrates 1311:huntingtin 1238:are human 1191:initiators 1187:amino acid 1160:-8 or -10. 1035:DNA damage 1025:DNA damage 898:a form of 735:See also: 698:Drosophila 694:C. elegans 654:See also: 645:Mechanisms 639:UK Biobank 621:Infections 614:DNA damage 512:astrocytes 80:Psychiatry 6811:Neurochip 6577:Cognitive 6502:Neurology 5819:Episodic/ 5697:Tauopathy 5648:Akathisia 5636:Myoclonus 5619:Athetosis 5551:Tauopathy 5002:Pharm Med 4403:(1): 90. 4219:205037169 4094:256193462 3733:241832253 3719:(5): 22. 3668:Neurology 3487:1943-0264 3350:208186566 3214:CiteSeerX 2401:Neurology 2164:859536969 2102:1559-0283 1811:Molecules 1547:(4): 20. 1195:effectors 1146:Apoptosis 1021:defense. 956:from the 884:ubiquitin 806:found in 670:glutamine 539:known as 321:(LRRK2), 304:ubiquitin 242:(APP), a 76:Neurology 71:Specialty 6890:Category 6774:Concepts 6720:Neurolaw 6452:Clinical 6185:SMALED2B 6180:SMALED2A 5877:Migraine 5869:Headache 5835:epilepsy 5831:Seizures 5689:Dementia 5592:Dystonia 5262:Fox News 5244:22951439 5150:54334969 5142:15080893 5107:18352830 5058:39817779 5050:18790460 4976:19739739 4968:19960212 4916:16200193 4867:33018251 4859:12728264 4824:17069462 4773:20345246 4724:21550379 4670:25033177 4618:27663141 4566:28785371 4515:18333761 4480:29947927 4429:33771206 4377:18957430 4326:18957428 4275:18957429 4211:18401401 4159:35925897 4098:Archived 4086:36690772 4042:36669485 4033:10079561 3987:28438892 3938:26385091 3856:17051205 3808:31 March 3782:31 March 3757:31 March 3698:32300063 3642:30783219 3546:17453052 3505:25877220 3448:17435754 3399:17435755 3342:31743477 3300:32973334 3238:18490361 3187:31885862 3161:: 2100. 3070:23768628 3021:32675289 2960:10923984 2900:17965655 2851:18279698 2785:28195358 2735:33274040 2679:26601739 2630:20693280 2574:18558852 2521:26718594 2486:25739126 2478:15004691 2469:11138910 2429:25017332 2421:15184601 2386:15787600 2351:25376584 2343:12927332 2308:16822978 2259:54359937 2215:34093032 2129:12934968 2007:17051206 1929:17051204 1843:31013638 1792:29513402 1743:34829716 1692:38585882 1683:10996678 1622:35163773 1571:28716886 1490:See also 1224:necrosis 1183:Caspases 1158:caspases 882:protein 707:and the 690:nematode 650:Genetics 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1613:8837071 1562:5880171 1496:Amyloid 1439:Dimebon 1369:of the 1273:binding 1256:termed 1240:enzymes 1172:nucleus 1103:kinesin 1037:in the 1007:Neurons 617:speed. 501:C9orf72 433:of the 375:frontal 252:enzymes 248:cleaved 203:of the 201:atrophy 195:in the 189:neurons 93:neurons 57:Normal 6638:fields 5916:Stroke 5730:Pick's 5657:Tremor 5624:Chorea 5242: 5232: 5191: 5148: 5140: 5105: 5095: 5056: 5048: 4974: 4966: 4914: 4904: 4865: 4857: 4822: 4812: 4771: 4761: 4722: 4712: 4668: 4658: 4640:Neuron 4616: 4606: 4564: 4554: 4513: 4478: 4468: 4427: 4417: 4375: 4365: 4324: 4314: 4273: 4263: 4217: 4209: 4181:Nature 4157: 4147: 4092: 4084: 4058:Nature 4040: 4030: 4010:Neuron 3985: 3975: 3936: 3926: 3885: 3862: 3854: 3828:Nature 3731: 3696: 3686: 3640: 3630: 3552: 3544: 3503: 3493: 3485: 3446: 3436: 3397: 3387: 3348: 3340: 3298: 3288: 3236: 3216: 3185: 3175: 3122: 3068: 3058: 3019: 3009: 2958: 2948: 2898: 2888: 2849: 2812: 2783: 2773: 2733: 2723: 2677: 2667: 2628: 2618: 2572: 2519: 2484: 2476: 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