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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Brain protein oxidation in age-related neurodegenerative disorders that are associated with aggregated proteins.
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Aggregated and monomeric α-synuclein bind to the S6′ proteasomal protein and inhibit proteasomal function
Heather Snyder,Kwame Mensah,Catherine Theisler,J.M. Lee,Andreas T Matouschek,Benjamin Wolozin +5 more
TL;DR: Binding studies demonstrate that both aggregated and monomeric α-synuclein selectively bind to the proteasomal protein S6′, a subunit of the 19 S cap, which suggests that proteasomesomal inhibition by aggregated α- synuclein could be mediated by interaction with S 6′.
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A novel α-synuclein mutation A53E associated with atypical multiple system atrophy and Parkinson's disease-type pathology
Petra Pasanen,Liisa Myllykangas,Maija Siitonen,Anna Raunio,Seppo Kaakkola,Jukka Lyytinen,Pentti J. Tienari,Minna Pöyhönen,Minna Pöyhönen,Anders Paetau +9 more
TL;DR: The results suggest that the novel SNCA A53E substitution is a causative mutation resulting clinically in parkinsonism and pathologically in severe multiple system atrophy- and PD-type phenotype.
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Axon pathology in Parkinson's disease and Lewy body dementia hippocampus contains alpha-, beta-, and gamma-synuclein.
TL;DR: This work shows that in PD and DLB, but not normal brains, antibodies to alphaS and betaS reveal novel presynaptic axon terminal pathology in the hippocampus, hilar, and CA2/3 regions, whereas antibodies to gammaS detect previously unrecognized axonal spheroid-like lesions in the hippocampal dentate molecular layer.
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Linkage of a prion protein missense variant to Gerstmann–Sträussler syndrome
Karen Hsiao,Harry F. Baker,Timothy J. Crow,Mark Poulter,Frank Owen,Joseph D. Terwilliger,David Westaway,Jurg Ott,Jurg Ott,Stanley B. Prusiner +9 more
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