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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Structural characterization of copper(II) binding to α-synuclein: Insights into the bioinorganic chemistry of Parkinson's disease
Rodolfo M. Rasia,Carlos W. Bertoncini,Derek Marsh,Wolfgang Hoyer,Dmitry I. Cherny,Markus Zweckstetter,Christian Griesinger,Thomas M. Jovin,Claudio O. Fernández +8 more
TL;DR: It is demonstrated here that Cu(II) ions are effective in accelerating AS aggregation at physiologically relevant concentrations without altering the resultant fibrillar structures.
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α-Synucleinopathy associated with G51D SNCA mutation: a link between Parkinson's disease and multiple system atrophy?
Aoife Kiely,Yasmine T. Asi,Eleanna Kara,Patricia Limousin,Patricia Limousin,Helen Ling,Patrick A. Lewis,Patrick A. Lewis,Christos Proukakis,Niall Quinn,Andrew J. Lees,John Hardy,Tamas Revesz,Henry Houlden,Janice L. Holton +14 more
TL;DR: A British family with young-onset Parkinson’s disease and a G51D SNCA mutation that segregates with the disease and post-mortem brain examination of the proband revealed atrophy affecting frontal and temporal lobes, which could aid in understanding of α-synuclein biology and its impact on disease phenotype.
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Parkin Suppresses Dopaminergic Neuron-Selective Neurotoxicity Induced by Pael-R in Drosophila
TL;DR: This study shows in an organismal system that panneuronal expression of Parkin substrate Pael-R causes age-dependent selective degeneration of Drosophila dopaminergic neurons and suggests that manipulating Parkin expression may provide a novel avenue of PD therapy.
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Neurotoxin-induced degeneration of dopamine neurons in Caenorhabditis elegans
TL;DR: It is demonstrated that agents that interfere with DAT function protect against 6-OHDA toxicity, and 6- OHDA-triggered neural degeneration does not require the CED-3/CED-4 cell death pathway, but is abolished by the genetic disruption of the C. elegans DAT.
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Sensitivity to oxidative stress in DJ-1-deficient dopamine neurons: an ES- derived cell model of primary Parkinsonism.
Cécile Martinat,Shoshana Shendelman,Alan Jonason,Thomas Leete,M. Flint Beal,Lichuan Yang,Thomas Floss,Asa Abeliovich +7 more
TL;DR: It is found that dopamine neurons derived from in vitro–differentiated DJ-1-deficient embryonic stem cells display decreased survival and increased sensitivity to oxidative stress, and the utility of genetically modified embryonic stem cell–derived neurons as cellular models of neuronal disorders is demonstrated.
References
More filters
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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