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Despite being considered the archetypal non-genetic neurological disorder, genetic analysis of Parkinson's disease has shown that there are at least three genetic loci. Furthermore, these analyses have suggested that the phenotype of the... more
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      GeneticsMultiple System AtrophyAlpha SynucleinBiological Sciences
The aggregation of R-synuclein is believed to play an important role in the pathogenesis of Parkinson's disease as well as other neurodegenerative disorders ("synucleinopathies"). However, the function of R-synuclein under physiologic and... more
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      BiochemistryElectron MicroscopyKineticsSynchrotron Radiation
The misfolding and aggregation of the protein asynuclein (a-syn), which results in the formation of amyloid fibrils, is involved in the pathogenesis of Parkinsons disease and other synucleinopathies. The emergence of amyloid toxicity is... more
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      Protein FoldingMagnetic Resonance SpectroscopyProtein EngineeringAlpha Synuclein
Latrepirdine (Dimebon) is a pro-neurogenic, antihistaminic compound that has yielded mixed results in clinical trials of mild to moderate Alzheimer's disease, with a dramatically positive outcome in a Russian clinical trial that was... more
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      CognitionAutophagyMolecular PsychiatryTransgenic Mice
Growing evidence suggests that oxidative stress is involved in the neuronal degeneration and can promote the aggregation of α-synuclein. However, the role of α-synuclein under physiological and pathological conditions remains poorly... more
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      Oxidative StressAlpha SynucleinProtein TranslocationDopamine
Genome-wide screens were performed in yeast to identify genes that enhance the toxicity of a mutant huntingtin fragment or of ␣-synuclein. Of 4850 haploid mutants containing deletions of nonessential genes, 52 were identified that were... more
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      Protein FoldingScienceOxidative StressMedicine
Rotenone, a mitochondrial complex 1 inhibitor, causes oxidative damage via production of reactive oxygen species. We examined the pathophysiology of neuronal and glial cells of the nigrostriatal pathway following unilateral infusion of... more
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      Cognitive ScienceImmunohistochemistryApoptosisAlpha Synuclein
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      CalciumOxidative StressAlpha SynucleinNeurotoxicology
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      ElectrochemistryNeurochemistryOxidative StressMitochondria
A-Synuclein, a protein implicated in neurodegenerative diseases and of elusive physiological function owes its name to an observed presence in presynaptic and nuclear compartments. However, its nuclear localisation has remained... more
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      Cognitive ScienceAlpha SynucleinHippocampusMutation
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      ImmunohistochemistryTreatment OutcomeAlpha SynucleinDisease Progression
The aggregation of R-synuclein (AS) is a critical step in the etiology of Parkinson's disease (PD) and other neurodegenerative synucleinopathies. Protein-metal interactions play a critical role in AS aggregation and might represent the... more
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      KineticsAlpha SynucleinSequence alignmentCircular Dichroism
Protein misfolding causes serious biological malfunction, resulting in diseases including Alzheimer's disease, Parkinson's disease and cataract. Molecules which inhibit protein misfolding are a promising avenue to explore as therapeutics... more
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      Protein FoldingAlpha SynucleinAmyloidCatalase
Mitochondrial and lysosomal dysfunction have been implicated in substantia nigra dopaminergic neurodegeneration in Parkinson's disease (PD), but how these pathways are linked in human neurons remains unclear. Here we studied dopaminergic... more
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      ScienceOxidative StressMitochondriaMultidisciplinary
Abnormal accumulation and propagation of the neuronal protein α-synuclein has been hypothesized to underlie the pathogenesis of Parkinson's disease, dementia with Lewy bodies and multiple system atrophy. Here we report a de... more
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      Animal BehaviorBiologyDrug DiscoveryMedicine
Abstract—The dementia,with,Lewy bodies,(DLB) Consortium,has,revised,criteria for the clinical and,pathologic,diagno- sis of DLB incorporating,new,information,about,the core clinical features,and,suggesting,improved,methods,to assess
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      Cognitive ScienceNeurologyElectroencephalographyImmunohistochemistry
Alzheimer's disease (AD), Pick's disease (PiD), progressive supranuclear palsy (PSP), corticobasal degeneration (CBD) and dementia with Lewy bodies (DLB) are diseases associated with the accumulation of tau or a-synuclein. In AD,... more
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      Progressive Supranuclear PalsyImmunohistochemistryConfocal MicroscopyNeurodegenerative Diseases
Here we show that ␣-synuclein, a major constituent of Lewy bodies, induces inflammation in human microglial and human THP-1 cells. Secretions from such stimulated THP-1 cells contain increased levels of IL-1␤ and TNF-␣. When stimulated by... more
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      Oxidative StressNeurobiologySignal TransductionAlpha Synuclein
Currently there are no disease-modifying alternatives for the treatment of most neurodegenerative disorders. The available therapies for diseases such as Parkinson's disease (PD), PD dementia (PDD), dementia with Lewy bodies (DLB), and... more
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      Neurodegenerative DiseasesAlpha SynucleinCombination drug therapy
Parkinson's disease is characterized by a progressive loss of dopaminergic neurons in the substantia nigra zona compacta, and in other sub-cortical nuclei associated with a widespread occurrence of Lewy bodies. The cause of cell death in... more
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      Cognitive ScienceStem CellApoptosisTransgenic Mice
Parkinson's disease (PD), one of the most common neurodegenerative diseases, is a multifactorial disease caused by both genetic and environmental factors. Although most patients suffering from PD have a sporadic disease, several genetic... more
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      GeneticsCognitive ScienceMolecular NeuroscienceDrosophila melanogaster
Protein aggregation causes many devastating neurological and systemic diseases and represents a major problem in the preparation of recombinant proteins in biotechnology. Major advances in understanding the causes of this phenomenon have... more
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      AlgorithmsProtein FoldingComputational BiologyForecasting
The role of neuroinflammation and the adaptive immune system in PD (Parkinson's disease) has been the subject of intense investigation in recent years, both in animal models of parkinsonism and in post-mortem PD brains. However, how these... more
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      Alpha SynucleinBrainMicrogliaNeurons
Parkinson’s disease (PD) is a common neurodegenerative disorder. Neuronal cell death in PD is still poorly understood, despite a wealth of potential pathogenic mechanisms and pathways. Defects in several cellular systems have been... more
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      Cell CycleApoptosisNeuronal cell deathNeuroprotection
Parkinson's disease (PD) is a common chronic progressive neurodegenerative disorder in elderly people. A consistent neurochemical abnormality in PD is degeneration of dopaminergic neurons in substantia nigra pars compacta, leading to a... more
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      Alpha SynucleinDopamineIsoenzymesCNS
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      Protein FoldingAlpha SynucleinBiological SciencesMolecular chaperones
Classically, Parkinson's disease (PD) is linked to dopamine neuron death in the substantia nigra pars compacta. Intracytoplasmic protein inclusions named Lewy bodies, and corresponding Lewy neurites found in neuronal processes, are also... more
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      Protein FoldingAlpha SynucleinAmyotrophic Lateral SclerosisBiological Sciences
Parkinson's disease (PD) is a neurodegenerative movement disorder characterized by the degeneration and progressive loss of dopaminergic neurons in the substantia nigra pars compacta. It has been suggested that oxidative stress plays a... more
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      InflammationOxidative StressNeuroprotectionSignal Transduction
Developing effective treatments for neurodegenerative diseases is one of the greatest medical challenges of the 21st century. Although many of these clinical entities have been recognized for more than a hundred years, it is only during... more
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      Molecular MedicineAlpha SynucleinMolecularBrain
Dementia with Lewy bodies (DLB) is the second most common cause of neurodegenerative dementia in older people that has only been recognized in the past decade and that remains widely underdiagnosed. At postmortem examination, affected... more
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      Cognitive ScienceMagnetic Resonance ImagingDysarthriaAlpha Synuclein
Substantial evidence links α-synuclein, a small highly conserved presynaptic protein with unknown function, to both familial and sporadic Parkinson's disease (PD). α-Synuclein has been identified as the major component of Lewy bodies and... more
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      Protein FoldingMolecular MechanicsAlpha SynucleinBiological Sciences
alpha-Synuclein is a highly conserved presynaptic protein with probable roles in normal synaptic development and plasticity as well as neurodegenerative disease, although its molecular function is not yet clear. To identify potential... more
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      Cognitive ScienceImmunohistochemistryWestern blottingAlpha Synuclein
Parkinson's disease (PD) is a common neurodegenerative disorder. The etiology of PD is likely due to combinations of environmental and genetic factors. In addition to the loss of neurons, including dopaminergic neurons in the... more
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      GeneticsCognitive ScienceAlpha SynucleinCell Death
Word すくみ足を伴う純粋無動症,進行性核上性麻痺(progressive supranuclear palsy; PSP) ,原発性進行性す くみ足(primary progressive freezing gait) ,歩行開始障害(gait ignition failure) 臨床症候群としての純粋無動症は,進行性核上性麻痺 (progressive supranuclear palsy; PSP)を合併するこ Present Gradual onset... more
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      PsychologyCognitive ScienceProgressive Supranuclear PalsyImmunohistochemistry
Manganism is a distinct medical condition from Parkinson's disease. Manganese exposure scenarios in the last century generally have changed from the acute, highlevel exposure conditions responsible for the occurrence of manganism to... more
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      ManganeseAlpha SynucleinWeldingConceptual Model
Parkinson's disease (PD) is the second most common neurodegenerative disorder after Alzheimer's disease. A progressive movement disorder typified by the production of bradykinesia, tremor, rigidity, and impairment of postural reflexes, PD... more
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      Alpha SynucleinBiological SciencesProtein KinasesParkinson Disease
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      GeneticsChemicalAlpha SynucleinAmyotrophic Lateral Sclerosis
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      Cognitive ScienceAlpha SynucleinNeuronsPrP
One of the key molecular events underlying the pathogenesis of Parkinson's disease (PD) is the aberrant misfolding and aggregation of the α-synuclein (αS) protein into higher-order oligomers that play a key role in neuronal dysfunction... more
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      MembranesMitochondriaAlpha SynucleinParkinson´s Disease
It is hoped that an understanding of the genetic basis of Parkinson's disease (PD) will lead to an appreciation of the molecular pathogenesis of disease, which in turn will highlight potential points of therapeutic intervention. It is... more
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      GeneticsAlpha SynucleinBiological SciencesMutation
Objective: Frontotemporal lobar degeneration (FTLD) encompasses a variety of clinicopathologic entities. The antemortem prediction of the underlying pathologic lesions is reputed to be difficult. This study sought to characterize... more
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      Cognitive ScienceNeurologySpeech DisordersAlpha Synuclein
Amyloid Precursor Protein serves a variety of physiological functions, including modulation of synaptic function, facilitation of neuronal growth and survival, protection against oxidative stress and surveillance against neuroactive... more
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      DementiaAlpha SynucleinClinical PracticeBrain
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      GeneticsDeep Brain StimulationAlpha SynucleinProtein Kinases
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      Protein FoldingFluorescence MicroscopyMultidisciplinaryAlpha Synuclein
Parkinson disease (PD) is a neurodegenerative disease characterised by progressive disturbances in motor, autonomic and psychiatric functions. Much has been learnt since the disease entity was established in 1817. Although there are well... more
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      Alpha SynucleinUbiquitinProtein KinasesMutation
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      Cognitive ScienceNeurodegenerative DiseasesAlpha SynucleinMolecular Neurobiology
Budding yeast Saccharomyces cerevisiae has proven to be a valuable model organism for studying fundamental cellular processes across the eukaryotic kingdom including man. In this respect, complementation assays, in which the yeast protein... more
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      Protein FoldingMedical MicrobiologyApoptosisMolecular Mechanics
Parkinson's disease patients exhibit progressive spreading of aggregated α-synuclein in the nervous system. This slow process follows a specific pattern in an inflamed tissue environment. Recent research suggests that prion-like... more
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      Cognitive ScienceInflammationAlpha SynucleinMolecular Neurobiology
a b s t r a c t a r t i c l e i n f o Keywords: Immunotherapy Neurodegenerative disease α-Synucleinopathies α-Synuclein Parkinson's disease Multiple system atrophy Immunotherapy is currently being intensively explored as much-needed... more
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      Neurodegenerative DiseasesAlpha SynucleinLBSCt