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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CHIP regulates leucine-rich repeat kinase-2 ubiquitination, degradation, and toxicity
Han Seok Ko,Rachel M. Bailey,Wanli W. Smith,Zhaohui Liu,Joo Ho Shin,Yun Il Lee,Yong Jie Zhang,Haibing Jiang,Christopher A. Ross,Darren J. Moore,Cam Patterson,Leonard Petrucelli,Ted M. Dawson,Valina L. Dawson +13 more
TL;DR: It is shown that the carboxyl terminus of HSP70-interacting protein (CHIP) binds, ubiquitinates, and promotes the ubiquitin proteasomal degradation of LRRK2, and that increasing CHIP E3 ligase activity and blocking HSP90 chaperone activity can prevent the deleterious effects of L RRK2.
Journal ArticleDOI
Multiple system atrophy: a sporadic synucleinopathy.
TL;DR: MSA and LBD are both synucleinopathies, and they may comprise different poles of a disease spectrum that includes sporadic disorders as well as genetically determined disorders such as familial Lewy body Parkinsonism.
Journal ArticleDOI
Association of Single-Nucleotide Polymorphisms of the Tau Gene With Late-Onset Parkinson Disease
Eden R. Martin,William K. Scott,Martha Nance,Ray L. Watts,Jean P. Hubble,William C. Koller,Kelly E. Lyons,Rajesh Pahwa,Matthew B. Stern,Amy Colcher,Bradley C. Hiner,Joseph Jankovic,William G. Ondo,Fred H. Allen,Christopher G. Goetz,Gary W. Small,Donna Masterman,Frank L. Mastaglia,Nigel G. Laing,Jeffrey M. Stajich,Robert C. Ribble,Michael W. Booze,Allison R. Rogala,Michael A. Hauser,Fengyu Zhang,Rachel A. Gibson,Lefkos T. Middleton,Allen D. Roses,Jonathan L. Haines,Burton L. Scott,Margaret A. Pericak-Vance,Jeffery M. Vance +31 more
TL;DR: This integrated approach of genetic linkage and positional association analyses implicates tau as a susceptibility gene for idiopathic PD.
Journal Article
Proteolytic stress: A unifying concept for the etiopathogenesis of Parkinson's disease. Discussion
TL;DR: The etiopathogenesis of Parkinson's disease (PD) has been elusive as mentioned in this paper, and several lines of evidence have converged to suggest that defects in the ubiquitin-proteasome system and proteolytic stress underlie nigral pathology in both familial and sporadic forms of the illness.
Journal ArticleDOI
α-Synuclein produces a long-lasting increase in neurotransmitter release
Shumin Liu,Ipe Ninan,Irina Antonova,Fortunato Battaglia,Fabrizio Trinchese,Archana Narasanna,Nikolai Kolodilov,William T. Dauer,Robert D. Hawkins,Ottavio Arancio +9 more
TL;DR: It is found that long‐lasting potentiation of synaptic transmission between cultured hippocampal neurons is accompanied by an increase in the number of α‐synuclein clusters, and inhibitors of NO‐synthase block this increase, supporting the hypothesis that NO is involved in the enhancement of the number.
References
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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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