Source:http://linkedlifedata.com/resource/pubmed/id/15909996
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
21
|
| pubmed:dateCreated |
2005-5-24
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| pubmed:abstractText |
Alpha-synuclein (alpha-syn) is a major protein component of the neuropathological hallmarks of Parkinson's disease and related neurodegenerative disorders termed synucleinopathies. Neither the mechanism of alpha-syn fibrillization nor the degradative process for alpha-syn has been elucidated. Previously, we showed that wild-type, mutated, and fibrillar alpha-syn proteins are substrates of calpain I in vitro. In this study, we demonstrate that calpain-mediated cleavage near and within the middle region of soluble alpha-syn with/without tyrosine nitration and oxidation generates fragments that are unable to self-fibrillize. More importantly, these fragments prevent full-length alpha-syn from fibrillizing. Calpain-mediated cleavage of alpha-syn fibrils composed of wild-type or nitrated alpha-syn generate C-terminally truncated fragments that retain their fibrillar structure and induce soluble full-length alpha-syn to co-assemble. Therefore, calpain-cleaved soluble alpha-syn inhibits fibrillization, whereas calpain-cleaved fibrillar alpha-syn promotes further co-assembly. These results provide insight into possible disease mechanisms underlying synucleinopathies since the formation of alpha-syn fibrils could be causally linked to the onset/progression of these disorders.
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| pubmed:language |
eng
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| pubmed:journal | |
| pubmed:citationSubset |
IM
|
| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/3-nitrotyrosine,
http://linkedlifedata.com/resource/pubmed/chemical/Calpain,
http://linkedlifedata.com/resource/pubmed/chemical/Chymotrypsin,
http://linkedlifedata.com/resource/pubmed/chemical/Nerve Tissue Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Nitrates,
http://linkedlifedata.com/resource/pubmed/chemical/Peptide Fragments,
http://linkedlifedata.com/resource/pubmed/chemical/Peroxynitrous Acid,
http://linkedlifedata.com/resource/pubmed/chemical/Recombinant Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/SNCA protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Synucleins,
http://linkedlifedata.com/resource/pubmed/chemical/Tyrosine,
http://linkedlifedata.com/resource/pubmed/chemical/alpha-Synuclein
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| pubmed:status |
MEDLINE
|
| pubmed:month |
May
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| pubmed:issn |
0006-2960
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| pubmed:author | |
| pubmed:issnType |
Print
|
| pubmed:day |
31
|
| pubmed:volume |
44
|
| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
|
| pubmed:pagination |
7818-29
|
| pubmed:dateRevised |
2006-11-15
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| pubmed:meshHeading |
pubmed-meshheading:15909996-Calpain,
pubmed-meshheading:15909996-Chymotrypsin,
pubmed-meshheading:15909996-Humans,
pubmed-meshheading:15909996-Hydrolysis,
pubmed-meshheading:15909996-Microscopy, Immunoelectron,
pubmed-meshheading:15909996-Nerve Degeneration,
pubmed-meshheading:15909996-Nerve Tissue Proteins,
pubmed-meshheading:15909996-Nitrates,
pubmed-meshheading:15909996-Parkinson Disease,
pubmed-meshheading:15909996-Peptide Fragments,
pubmed-meshheading:15909996-Peroxynitrous Acid,
pubmed-meshheading:15909996-Recombinant Proteins,
pubmed-meshheading:15909996-Solubility,
pubmed-meshheading:15909996-Synucleins,
pubmed-meshheading:15909996-Tyrosine,
pubmed-meshheading:15909996-alpha-Synuclein
|
| pubmed:year |
2005
|
| pubmed:articleTitle |
Cleavage of alpha-synuclein by calpain: potential role in degradation of fibrillized and nitrated species of alpha-synuclein.
|
| pubmed:affiliation |
Department of Neurology, University of Pennsylvania and The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania 19104, USA.
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| pubmed:publicationType |
Journal Article,
Comparative Study,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't,
Research Support, N.I.H., Extramural
|