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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Journal ArticleDOI
Parkin genetics: one model for Parkinson's disease.
TL;DR: Comparing and contrast PD and AR-JP is compared and compared and the implications of recent data about parkin's genomic organization, regulation and function are discussed.
Journal ArticleDOI
Mechanism of membrane interaction and disruption by α-synuclein.
Nicholas P. Reynolds,Alice Soragni,Michael Rabe,Dorinel Verdes,Ennio Liverani,Stephan Handschin,Roland Riek,Stefan Seeger +7 more
TL;DR: Both the wild-type and the two mutant forms of α-synuclein studied, namely, the familiar variant A53T and the designed highly toxic variant E57K, were found to follow the same mechanism of polymerization and membrane damage.
Journal ArticleDOI
Accumulation of oligomer-prone α-synuclein exacerbates synaptic and neuronal degeneration in vivo.
Edward Rockenstein,Silke Nuber,Cassia R. Overk,Kiren Ubhi,Michael Mante,Christina Patrick,Anthony Adame,Margarita Trejo-Morales,Juan Gerez,Paola Picotti,Poul Henning Jensen,Silvia Campioni,Roland Riek,Jürgen Winkler,Fred H. Gage,Beate Winner,Eliezer Masliah +16 more
TL;DR: The hypothesis that accumulating oligomeric α-synuclein may mediate early synaptic pathology in Parkinson's disease and dementia with Lewy bodies by disrupting synaptic vesicles is supported.
Journal ArticleDOI
Spinocerebellar ataxia type 2 with parkinsonism in ethnic Chinese.
Katrina Gwinn-Hardy,Chen Jy,Liu Hc,Liu Ty,Boss M,W. Seltzer,Amanda Adam,AB Singleton,Koroshetz W,Cheryl Waters,John Hardy,Matthew J. Farrer +11 more
TL;DR: Patients presenting with a family history of parkinsonism, including familial progressive supranuclear palsy and PD, should be tested for the spinocerebellar ataxia type 2 expansion.
Journal ArticleDOI
Polo-like Kinase 2 (PLK2) Phosphorylates α-Synuclein at Serine 129 in Central Nervous System
Kelly J. Inglis,David Chereau,Elizabeth F. Brigham,San-San Chiou,Susanne Schöbel,Normand Frigon,Mei Yu,Russell J. Caccavello,Seth Nelson,Ruth Motter,Sarah Wright,David Chian,Pamela Santiago,Ferdie Soriano,Carla Ramos,Kyle Powell,Jason Goldstein,Michael Babcock,Ted Yednock,Frederique Bard,Guriqbal S. Basi,Hing Sham,Tamie J. Chilcote,Lisa McConlogue,Irene Griswold-Prenner,John P. Anderson +25 more
TL;DR: Evidence is submitted that polo-like kinase 2 (PLK2), also known as serum-inducible kinase or SNK, is a principle contributor to α-synuclein phosphorylation at Ser-129 in neurons in neurons.
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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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