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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
3
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pubmed:dateCreated |
2003-8-29
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pubmed:abstractText |
Two mutations in alpha-synuclein, the main constituent of Lewy bodies, have been identified in familial Parkinson's disease. We have stereotactically injected lentiviral vectors encoding wild-type and A30P mutant human alpha-synuclein in different brain regions (striatum, substantia nigra, amygdala) of mice. Overexpression of alpha-synuclein induced time-dependent neuropathological changes reminiscent of Lewy pathology: abnormal accumulation of alpha-synuclein in cell bodies and neurites, alpha-synuclein-positive neuritic varicosities and cytoplasmic inclusions that stained with ubiquitin antibodies and became larger and more frequent with time. After one year, alpha-synuclein- and ubiquitin-positive neurons displayed a degenerative morphology and a significant loss of alpha-synuclein-positive cells was observed. Similar findings were observed with both the wild-type and the A30P mutant form of alpha-synuclein and this in different brain regions. This indicates that overexpression of alpha-synuclein is sufficient to induce Lewy-like pathology and neurodegeneration and that this effect is not restricted to dopaminergic cells. Our data also demonstrate the use of lentiviral vectors to create animal models for neurodegenerative diseases.
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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 |
Jul
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pubmed:issn |
1015-6305
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:volume |
13
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
364-72
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pubmed:dateRevised |
2006-11-15
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pubmed:meshHeading |
pubmed-meshheading:12946025-Amygdala,
pubmed-meshheading:12946025-Animals,
pubmed-meshheading:12946025-Blotting, Western,
pubmed-meshheading:12946025-Cell Count,
pubmed-meshheading:12946025-Corpus Striatum,
pubmed-meshheading:12946025-Disease Models, Animal,
pubmed-meshheading:12946025-Female,
pubmed-meshheading:12946025-Humans,
pubmed-meshheading:12946025-Immunohistochemistry,
pubmed-meshheading:12946025-Inclusion Bodies, Viral,
pubmed-meshheading:12946025-Lentivirus Infections,
pubmed-meshheading:12946025-Lewy Body Disease,
pubmed-meshheading:12946025-Mice,
pubmed-meshheading:12946025-Mice, Inbred C57BL,
pubmed-meshheading:12946025-Microscopy, Confocal,
pubmed-meshheading:12946025-Mutation,
pubmed-meshheading:12946025-Nerve Tissue Proteins,
pubmed-meshheading:12946025-Neurites,
pubmed-meshheading:12946025-Neuroblastoma,
pubmed-meshheading:12946025-Neurodegenerative Diseases,
pubmed-meshheading:12946025-Neurons,
pubmed-meshheading:12946025-Substantia Nigra,
pubmed-meshheading:12946025-Synucleins,
pubmed-meshheading:12946025-Time Factors,
pubmed-meshheading:12946025-Transduction, Genetic,
pubmed-meshheading:12946025-Tumor Cells, Cultured,
pubmed-meshheading:12946025-Tyrosine 3-Monooxygenase,
pubmed-meshheading:12946025-Ubiquitin,
pubmed-meshheading:12946025-alpha-Synuclein
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pubmed:year |
2003
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pubmed:articleTitle |
Neuropathology and neurodegeneration in rodent brain induced by lentiviral vector-mediated overexpression of alpha-synuclein.
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pubmed:affiliation |
Gene Therapy Program, Katholieke Universiteit Leuven, Leuven, Belgium.
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pubmed:publicationType |
Journal Article,
Comparative Study,
Research Support, Non-U.S. Gov't
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