An examination of alpha B-crystallin as a modifier of SOD1 aggregate pathology and toxicity in models of familial amyotrophic lateral sclerosis.

ABSTRACT: Amyotrophic lateral sclerosis is a progressively paralytic neurodegenerative disease that can be caused by mutations in Cu,Zn-superoxide dismutase 1 (SOD1). Transgenic mice that over-express mutant SOD1 develop paralysis and accumulate aggregates of mutant protein in the brainstem and spinal cord. The present study uses a cell culture model to demonstrate alpha B-crystallin is capable of reducing aggregation of mutant SOD1. To test the role of alpha B-crystallin in modulating SOD1 aggregation in vivo, alpha B-crystallin deficient mice were bred to mice expressing two different SOD1 mutants (G37R and L126Z). Although completely eliminating alpha B-crystallin reduced the interval to disease endstage by 20-30 days in mice expressing either mutant, there were no detectable changes in the level

SUBMITTER: Karch CM 

PROVIDER: S-EPMC3971727 | biostudies-literature | 2010 Jun

REPOSITORIES: biostudies-literature