|
rdf:type |
|
|
lifeskim:mentions |
|
|
pubmed:issue |
42
|
|
pubmed:dateCreated |
2002-10-15
|
|
pubmed:abstractText |
Huntington's disease (HD) is caused by a polyglutamine expansion in the amino-terminal region of huntingtin. Mutant huntingtin is proteolytically cleaved by caspases, generating amino-terminal aggregates that are toxic for cells. The addition of calpains to total brain homogenates also leads to cleavage of wild-type huntingtin, indicating that proteolysis of mutant and wild-type huntingtin may play a role in HD. Here we report that endogenous wild-type huntingtin is promptly cleaved by calpains in primary neurons. Exposure of primary neurons to glutamate or 3-nitropropionic acid increases intracellular calcium concentration, leading to loss of intact full-length wild-type huntingtin. This cleavage could be prevented by calcium chelators and calpain inhibitors. Degradation of wild-type huntingtin by calcium-dependent proteases thus occurs in HD neurons, leading to loss of wild-type huntingtin neuroprotective activity.
|
|
pubmed:language |
eng
|
|
pubmed:journal |
|
|
pubmed:citationSubset |
IM
|
|
pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/3-nitropropionic acid,
http://linkedlifedata.com/resource/pubmed/chemical/Calcimycin,
http://linkedlifedata.com/resource/pubmed/chemical/Calcium,
http://linkedlifedata.com/resource/pubmed/chemical/Calpain,
http://linkedlifedata.com/resource/pubmed/chemical/Glutamic Acid,
http://linkedlifedata.com/resource/pubmed/chemical/Hdh protein, rat,
http://linkedlifedata.com/resource/pubmed/chemical/Ionophores,
http://linkedlifedata.com/resource/pubmed/chemical/Nerve Tissue Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Nitro Compounds,
http://linkedlifedata.com/resource/pubmed/chemical/Nuclear Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Propionic Acids,
http://linkedlifedata.com/resource/pubmed/chemical/m-calpain
|
|
pubmed:status |
MEDLINE
|
|
pubmed:month |
Oct
|
|
pubmed:issn |
0021-9258
|
|
pubmed:author |
|
|
pubmed:issnType |
Print
|
|
pubmed:day |
18
|
|
pubmed:volume |
277
|
|
pubmed:owner |
NLM
|
|
pubmed:authorsComplete |
Y
|
|
pubmed:pagination |
39594-8
|
|
pubmed:dateRevised |
2006-11-15
|
|
pubmed:meshHeading |
pubmed-meshheading:12200414-Animals,
pubmed-meshheading:12200414-Blotting, Western,
pubmed-meshheading:12200414-Brain,
pubmed-meshheading:12200414-Calcimycin,
pubmed-meshheading:12200414-Calcium,
pubmed-meshheading:12200414-Calpain,
pubmed-meshheading:12200414-Cell-Free System,
pubmed-meshheading:12200414-Cells, Cultured,
pubmed-meshheading:12200414-Densitometry,
pubmed-meshheading:12200414-Glutamic Acid,
pubmed-meshheading:12200414-Ionophores,
pubmed-meshheading:12200414-Nerve Tissue Proteins,
pubmed-meshheading:12200414-Neurons,
pubmed-meshheading:12200414-Nitro Compounds,
pubmed-meshheading:12200414-Nuclear Proteins,
pubmed-meshheading:12200414-Propionic Acids,
pubmed-meshheading:12200414-Protein Binding,
pubmed-meshheading:12200414-Rats,
pubmed-meshheading:12200414-Rats, Sprague-Dawley,
pubmed-meshheading:12200414-Time Factors
|
|
pubmed:year |
2002
|
|
pubmed:articleTitle |
Calcium-dependent cleavage of endogenous wild-type huntingtin in primary cortical neurons.
|
|
pubmed:affiliation |
Department of Pharmacological Sciences and Center of Excellence on Neurodegenerative Diseases, University of Milan, Milano, Italy.
|
|
pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
|
