Assessing the role of immuno-proteasomes in a mouse model of familial ALS.
Exp Neurol
; 206(1): 53-8, 2007 Jul.
Article
in En
| MEDLINE
| ID: mdl-17482163
ABSTRACT
The accumulation of protein aggregates is thought to be an important component in the pathogenesis of mutant SOD1-induced disease. Mutant SOD1 aggregates appear to be cleared by proteasomes, at least in vitro, suggesting a potentially important role for proteasome degradation pathways in vivo. G93A SOD1 transgenic mice show an increase in proteasome activity and induction of immuno-proteasome subunits within spinal cord as they develop neurological symptoms. To determine what role immuno-proteasomes may have in mutant SOD1-induced disease, we crossed G93A SOD1 transgenic mice with LMP2-/- mice to obtain G93A SOD1 mice lacking the LMP2 immuno-proteasome subunit. G93A SOD1/LMP2-/- mice show significant reductions in proteasome function within spinal cord compared to G93A SOD1 mice. However, G93A SOD1/LMP2-/- mice show no change in motor function decline, or survival compared to G93A SOD1 mice. These results indicate that the loss of immuno-proteasome function in vivo does not significantly alter mutant SOD1-induced disease.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Spinal Cord
/
Superoxide Dismutase
/
Cysteine Endopeptidases
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Proteasome Endopeptidase Complex
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Amyotrophic Lateral Sclerosis
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Motor Neurons
Limits:
Animals
/
Humans
Language:
En
Journal:
Exp Neurol
Year:
2007
Document type:
Article
Affiliation country:
Estados Unidos