Destabilizing protein polymorphisms in the genetic background direct phenotypic expression of mutant SOD1 toxicity.

ABSTRACT: Genetic background exerts a strong modulatory effect on the toxicity of aggregation-prone proteins in conformational diseases. In addition to influencing the misfolding and aggregation behavior of the mutant proteins, polymorphisms in putative modifier genes may affect the molecular processes leading to the disease phenotype. Mutations in SOD1 in a subset of familial amyotrophic lateral sclerosis (ALS) cases confer dominant but clinically variable toxicity, thought to be mediated by misfolding and aggregation of mutant SOD1 protein. While the mechanism of toxicity remains unknown, both the nature of the SOD1 mutation and the genetic background in which it is expressed appear important. To address this, we established a Caenorhabditis elegans model to systematically examine the aggregation

SUBMITTER: Gidalevitz T 

PROVIDER: S-EPMC2642731 | biostudies-literature | 2009 Mar

REPOSITORIES: biostudies-literature