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rdf:type |
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lifeskim:mentions |
umls-concept:C0012655,
umls-concept:C0013030,
umls-concept:C0015127,
umls-concept:C0017262,
umls-concept:C0185117,
umls-concept:C0205217,
umls-concept:C0285890,
umls-concept:C0596988,
umls-concept:C0600688,
umls-concept:C1314792,
umls-concept:C2911684
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pubmed:issue |
18
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pubmed:dateCreated |
2000-11-28
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pubmed:abstractText |
Mutations of the alpha-synuclein gene have been identified in autosomal dominant Parkinson's disease (PD). Transgenic mice overexpressing wild-type human alpha-synuclein develop motor impairments, intraneuronal inclusions and loss of dopaminergic terminals in the striatum. To study the mechanism of action through which mutant alpha-synuclein toxicity is mediated, we have generated stable, inducible cell models expressing wild-type or PD-associated mutant (G209A) alpha-synuclein in human-derived HEK293 cells. Increased expression of either wild-type or mutant alpha-synuclein resulted in the formation of cytoplasmic aggregates which were associated with the vesicular (including monoaminergic) compartment. Expression of mutant alpha-synuclein induced a significant increase in sensitivity to dopamine toxicity compared with the wild-type protein expression. These results provide an explanation for the preferential dopaminergic neuronal degeneration seen in both the PD G209A mutant alpha-synuclein families and suggest that similar mechanisms may underlie or contribute to cell death in sporadic PD.
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:month |
Nov
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pubmed:issn |
0964-6906
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
1
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pubmed:volume |
9
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
2683-9
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pubmed:dateRevised |
2006-11-15
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pubmed:meshHeading |
pubmed-meshheading:11063727-Blotting, Western,
pubmed-meshheading:11063727-Cell Death,
pubmed-meshheading:11063727-Cell Line,
pubmed-meshheading:11063727-Cell Size,
pubmed-meshheading:11063727-Dopamine,
pubmed-meshheading:11063727-Drug Toxicity,
pubmed-meshheading:11063727-Ecdysterone,
pubmed-meshheading:11063727-Gene Expression,
pubmed-meshheading:11063727-Genetic Predisposition to Disease,
pubmed-meshheading:11063727-Humans,
pubmed-meshheading:11063727-Immunohistochemistry,
pubmed-meshheading:11063727-Male,
pubmed-meshheading:11063727-Mutation,
pubmed-meshheading:11063727-Nerve Tissue Proteins,
pubmed-meshheading:11063727-Neurons,
pubmed-meshheading:11063727-Parkinson Disease,
pubmed-meshheading:11063727-Parkinson Disease, Secondary,
pubmed-meshheading:11063727-Synucleins,
pubmed-meshheading:11063727-Transfection,
pubmed-meshheading:11063727-alpha-Synuclein
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pubmed:year |
2000
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pubmed:articleTitle |
Expression of mutant alpha-synuclein causes increased susceptibility to dopamine toxicity.
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pubmed:affiliation |
University Department of Clinical Neurosciences, Royal Free and University College Medical School, London NW3 2PF, UK.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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