Mutation in the α-synuclein gene identified in families with Parkinson's disease
Mihael H. Polymeropoulos,Christian Lavedan,Elisabeth Leroy,Susan E. Ide,Anindya Dehejia,Amalia Dutra,Brian L. Pike,Holly Root,Jeffrey Rubenstein,Rebecca Boyer,Edward S. Stenroos,Settara C. Chandrasekharappa,Aglaia Athanassiadou,Theodore Papapetropoulos,William G. Johnson,Alice Lazzarini,Roger C. Duvoisin,Giuseppe Di Iorio,Lawrence I. Golbe,Robert L. Nussbaum +19 more
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TLDR
A mutation was identified in the α-synuclein gene, which codes for a presynaptic protein thought to be involved in neuronal plasticity, in the Italian kindred and in three unrelated families of Greek origin with autosomal dominant inheritance for the PD phenotype.Abstract:
Parkinson's disease (PD) is a common neurodegenerative disorder with a lifetime incidence of approximately 2 percent. A pattern of familial aggregation has been documented for the disorder, and it was recently reported that a PD susceptibility gene in a large Italian kindred is located on the long arm of human chromosome 4. A mutation was identified in the α-synuclein gene, which codes for a presynaptic protein thought to be involved in neuronal plasticity, in the Italian kindred and in three unrelated families of Greek origin with autosomal dominant inheritance for the PD phenotype. This finding of a specific molecular alteration associated with PD will facilitate the detailed understanding of the pathophysiology of the disorder.read more
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Monoubiquitylation of α-Synuclein by Seven in Absentia Homolog (SIAH) Promotes Its Aggregation in Dopaminergic Cells
Ruth Rott,Raymonde Szargel,Joseph Haskin,Vered Shani,Alla Shainskaya,Irena Manov,Esti Liani,Eyal Avraham,Simone Engelender +8 more
TL;DR: It is reported that the ubiquitin-protein isopeptide ligase seven in absentia homolog (SIAH) directly interacts with and monoubiquitylates α-synuclein and promotes its aggregation in vitro and in vivo, which is toxic to cells.
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Neuropsychological Characteristics of Dementia with Lewy Bodies and Parkinson’s Disease with Dementia: Differentiation, Early Detection, and Implications for “Mild Cognitive Impairment” and Biomarkers
TL;DR: Although heterogeneous cognitive changes may manifest earlier and more frequently than previously appreciated in Parkinson’s disease (PD), and executive deficits may be harbingers of dementia, the enthusiasm to uncritically extend the concept of mild cognitive impairment (MCI) to PD should be tempered.
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Alpha-synuclein overexpression and aggregation exacerbates impairment of mitochondrial functions by augmenting oxidative stress in human neuroblastoma cells.
TL;DR: It is shown that overexpression of alpha-synuclein A53T or A30P mutants or wild-type in human neuroblastoma cells augmented aggregates within the mitochondria of overexpressing cells suggest an important role for mitochondria in cellular responses to alpha- Synuclein.
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Expression changes of dopaminergic system-related genes in PC12 cells induced by manganese, silver, or copper nanoparticles
Jianyong Wang,Mohammed F. Rahman,Helen M. Duhart,Glenn D. Newport,Tucker A. Patterson,Richard C. Murdock,Saber M. Hussain,John J. Schlager,Syed F. Ali +8 more
TL;DR: Investigation of the potential neurotoxicity of manganese (Mn), silver (Ag), and copper (Cu) nanoparticles using the dopaminergic neuronal cell line, PC12, suggests Mn and Cu nanoparticles-induced dopamine depletion may share some common mechanisms associated with neurodegeneration.
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Monomeric Synucleins Generate Membrane Curvature
TL;DR: It is demonstrated that the levels of synucleins and endophilin A1 are reciprocally regulated and that they are functionally related and it is proposed to includesynucleins in the class of amphipathic helix-containing proteins that sense and generate membrane curvature.
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