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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Book ChapterDOI
Etiology, Pathogenesis, and Genetics of Parkinson’s Disease
Yoshikuni Mizuno,Nobutaka Hattori,Hideki Shimura,Tohru Kitada,Shin-ichiro Kubo,Mei Wang,Kenichi Sato,Toshiaki Suzuki,Tomoki Chiba,Keiji Tanaka,Shuichi Asakawa,Shinsei Minoshima,Nobuyoshi Shimizu +12 more
TL;DR: What can be learned from familial PD is discussed to explore the pathogenesis of sporadic PD and how to prevent it.
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Stable Isotope Labeling Kinetics in CNS Translational Medicine: Introduction to SILK Technology
Randall J. Bateman,Tim West,Kevin E. Yarasheski,Bruce W. Patterson,Brendan P. Lucey,John R. Cirrito,Sylvain Lehmann,Christophe Hirtz,Audrey Gabelle,Timothy M. Miller,Nicolas R. Barthélemy,Chihiro Sato,James G. Bollinger,Paul T. Kotzbauer,Katrina L. Paumier +14 more
TL;DR: This chapter will review recent advancements in the development and application of SILK for measuring the pathophysiology and drug development for CNS diseases and provide important insights into Alzheimer's disease Pathophysiology with altered synthesis and clearance of amyloid-beta, and drug effects on amyloids-beta.
References
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Journal ArticleDOI
Cloning of a gene bearing missense mutations in early-onset familial Alzheimer's disease
R. Sherrington,Evgeny I. Rogaev,Yan Liang,Ekaterina Rogaeva,G. Levesque,M. Ikeda,H. Chi,Chih-Ping Lin,Gavin Li,K. Holman,T. Tsuda,L. Mar,J. F. Foncin,Amalia C. Bruni,Mp Montesi,Sandro Sorbi,Innocenzo Rainero,Lorenzo Pinessi,L. Nee,Ilya Chumakov,Daniel A. Pollen,A. Brookes,Philippe Sanseau,R. Polinsky,Wilma Wasco,H. A. R. Da Silva,Jonathan L. Haines,Margaret A. Pericak-Vance,Rudolph E. Tanzi,A. D. Roses,Paul E. Fraser,Johanna M. Rommens,P. St. George-Hyslop +32 more
TL;DR: A minimal cosegregating region containing the AD3 gene is defined, and at least 19 different transcripts encoded within this region corresponds to a novel gene whose product is predicted to contain multiple transmembrane domains and resembles an integral membrane protein.
Journal ArticleDOI
Familial Alzheimer's disease in kindreds with missense mutations in a gene on chromosome 1 related to the Alzheimer's disease type 3 gene
Evgeny I. Rogaev,R. Sherrington,Ekaterina Rogaeva,G. Levesque,M. Ikeda,Yan Liang,H. Chi,Chih-Ping Lin,K. Holman,T. Tsuda,L. Mar,Sandro Sorbi,Benedetta Nacmias,Silvia Piacentini,Luigi Amaducci,Ilya Chumakov,David M. Cohen,Lars Lannfelt,Paul E. Fraser,Johanna M. Rommens,P. St. George-Hyslop +20 more
TL;DR: Analysis of the nucleotide sequence of the open reading frame of the E5-1 gene led to the discovery of two missense substitutions at conserved amino-acid residues in affected members of pedigrees with a form of familial AD that has a later age of onset than the AD3 subtype (5070 years versus 3060 years for AD3).
Journal ArticleDOI
Synuclein: a neuron-specific protein localized to the nucleus and presynaptic nerve terminal
TL;DR: An antiserum against purified cholinergic synaptic vesicles from Torpedo and expression screening was used to isolate a cDNA clone encoding synuclein, a 143 amino acid neuron-specific protein that is expressed only in nervous system tissue.
Journal ArticleDOI
Molecular cloning of cDNA encoding an unrecognized component of amyloid in Alzheimer disease
Kenji Uéda,Hisashi Fukushima,Eliezer Masliah,Yu Xia,Akihiko Iwai,Makoto Yoshimoto,Deborah A. C. Otero,Jun Kondo,Yasuo Ihara,Tsunao Saitoh +9 more
TL;DR: Primary structure predictions indicate that the NAC peptide sequence has a strong tendency to form beta-structures consistent with its association with amyloid, and the availability of the cDNA encoding full-length NACP should help to elucidate the mechanisms of amyloidsosis in AD.
Journal ArticleDOI
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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