Therapeutic approaches to spinal and bulbar muscular atrophy.

ABSTRACT: Spinal and bulbar muscular atrophy is a hereditary motor neuron disease caused by trinucleotide repeat expansion in the androgen receptor gene. The disease mechanism probably involves a toxic gain of function in the mutant protein, because other mutations that cause a loss of androgen receptor function result in a different phenotype and the mutant protein is toxic in mouse models. In these models, the toxicity is ligand-dependent and is associated with protein aggregation, as well as altered transcriptional regulation, axonal transport and mitochondrial function. Various therapeutic approaches have shown efficacy in mouse models, including androgen reduction, heat shock protein 90 (HSP90) inhibition and insulin-like growth factor (IGF)-1 overexpression. Clinical trials of androgen-reducin

SUBMITTER: Ranganathan S 

PROVIDER: S-EPMC2963653 | biostudies-literature | 2010 Nov

REPOSITORIES: biostudies-literature