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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Alpha-synuclein structure and Parkinson’s disease – lessons and emerging principles
TL;DR: This work attempts to reinterpret the literature, particularly in terms of how αS structure may relate to pathology, taking into account newly revealed structural information on both native and pathogenic forms of the αS protein, including recent solid state NMR and cryoEM fibril structures.
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THE GENETIC ARCHITECTURE OF ALZHEIMER’S DISEASE: BEYOND APP, PSENs AND APOE
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Investigation of α-Synuclein Fibril Structure by Site-directed Spin Labeling
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Serpinopathies and the conformational dementias
David A. Lomas,Robin W. Carrell +1 more
TL;DR: The recent recognition that mutations in a serpin can also result in late-onset dementia provides insights into changes that underlie other conformational diseases, such as the amyloidoses, the prion encephalopathies and Huntington and Alzheimer diseases.
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The role of stable α-synuclein oligomers in the molecular events underlying amyloid formation.
Nikolai Lorenzen,Søren B. Nielsen,Alexander K. Buell,Jørn Døvling Kaspersen,Paolo Arosio,Brian S. Vad,Wojciech Paslawski,Gunna Christiansen,Zuzana Valnickova-Hansen,Maria Andreasen,Jan J. Enghild,Jan Skov Pedersen,Christopher M. Dobson,Tuomas P. J. Knowles,Daniel E. Otzen +14 more
TL;DR: Two well-defined oligomeric species formed by the protein α-synuclein, whose aggregation is strongly implicated in the development of Parkinson's disease, are described and characterize in detail.
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Kenji Uéda,Hisashi Fukushima,Eliezer Masliah,Yu Xia,Akihiko Iwai,Makoto Yoshimoto,Deborah A. C. Otero,Jun Kondo,Yasuo Ihara,Tsunao Saitoh +9 more
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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
TL;DR: It is shown here that PrP codon 102 is linked to the putative gene for the syndrome in two pedigrees, providing the best evidence to date that this familial condition is inherited despite also being infectious, and that substitution of leucine for proline at PrPcodon 102 may lead to the development of Gerstmann–Sträussler syndrome.
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