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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
2
|
| pubmed:dateCreated |
1999-2-11
|
| pubmed:abstractText |
Mutations in the Cu/Zn-superoxide dismutase (SOD-1) gene underlie some familial cases of amyotrophic lateral sclerosis, a neurodegenerative disorder characterized by loss of cortical, brainstem, and spinal motor neurons. We present evidence that SOD-1 mutants alter the activity of molecular chaperones that aid in proper protein folding and targeting of abnormal proteins for degradation. In a cultured cell line (NIH 3T3), resistance to mutant SOD-1 toxicity correlated with increased overall chaperoning activity (measured by the ability of cytosolic extracts to prevent heat denaturation of catalase) as well as with up-regulation of individual chaperones/stress proteins. In transgenic mice expressing human SOD-1 with the G93A mutation, chaperoning activity was decreased in lumbar spinal cord but increased or unchanged in clinically unaffected tissues. Increasing the level of the stress-inducible chaperone 70-kDa heat shock protein by gene transfer reduced formation of mutant SOD-containing proteinaceous aggregates in cultured primary motor neurons expressing G93A SOD-1 and prolonged their survival. We propose that insufficiency of molecular chaperones may be directly involved in loss of motor neurons in this disease.
|
| pubmed:grant | |
| pubmed:language |
eng
|
| pubmed:journal | |
| pubmed:citationSubset |
IM
|
| pubmed:chemical | |
| pubmed:status |
MEDLINE
|
| pubmed:month |
Feb
|
| pubmed:issn |
0022-3042
|
| pubmed:author | |
| pubmed:issnType |
Print
|
| pubmed:volume |
72
|
| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
|
| pubmed:pagination |
693-9
|
| pubmed:dateRevised |
2009-11-19
|
| pubmed:meshHeading |
pubmed-meshheading:9930742-3T3 Cells,
pubmed-meshheading:9930742-Amyotrophic Lateral Sclerosis,
pubmed-meshheading:9930742-Animals,
pubmed-meshheading:9930742-Cell Survival,
pubmed-meshheading:9930742-Chaperonins,
pubmed-meshheading:9930742-Gene Expression Regulation, Enzymologic,
pubmed-meshheading:9930742-Gene Transfer Techniques,
pubmed-meshheading:9930742-HSP70 Heat-Shock Proteins,
pubmed-meshheading:9930742-Heat-Shock Response,
pubmed-meshheading:9930742-Humans,
pubmed-meshheading:9930742-Mice,
pubmed-meshheading:9930742-Mice, Transgenic,
pubmed-meshheading:9930742-Motor Neurons,
pubmed-meshheading:9930742-Mutation,
pubmed-meshheading:9930742-Neuroprotective Agents,
pubmed-meshheading:9930742-Spinal Cord,
pubmed-meshheading:9930742-Superoxide Dismutase,
pubmed-meshheading:9930742-Transfection,
pubmed-meshheading:9930742-Up-Regulation
|
| pubmed:year |
1999
|
| pubmed:articleTitle |
Up-regulation of protein chaperones preserves viability of cells expressing toxic Cu/Zn-superoxide dismutase mutants associated with amyotrophic lateral sclerosis.
|
| pubmed:affiliation |
Montreal Neurological Institute and Department of Neurology/Neurosurgery, McGill University, Quebec, Canada.
|
| pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't
|