Dysregulation of the proteasome increases the toxicity of ALS-linked mutant SOD1.

ABSTRACT: A hallmark of protein conformational disease, exemplified by neurodegenerative disorders, is the expression of misfolded and aggregated proteins. The relationship between protein aggregation and cellular toxicity is complex, and various models of experimental pathophysiology have often yielded conflicting or controversial results. In this study, we examined the biophysical properties of amyotrophic lateral sclerosis (ALS)-linked mutations of Cu/Zn superoxide dismutase 1 (SOD1) expressed in human tissue culture cells. Fluorescence correlation spectroscopy (FCS) and Förster resonance energy transfer (FRET) analyses revealed that changes in proteasome activity affected both the expression of FCS- and FRET-detected oligomers and cellular toxicity. Under normal conditions, highly aggregation-pr

SUBMITTER: Kitamura A 

PROVIDER: S-EPMC4207061 | biostudies-literature | 2014 Mar

REPOSITORIES: biostudies-literature