Complete suppression of Htt fibrilization and disaggregation of Htt fibrils by a trimeric chaperone complex.

ABSTRACT: Huntington's disease (HD) is a neurodegenerative disorder caused by an expanded CAG trinucleotide repeat in the huntingtin gene (HTT). Molecular chaperones have been implicated in suppressing or delaying the aggregation of mutant Htt. Using in vitro and in vivo assays, we have identified a trimeric chaperone complex (Hsc70, Hsp110, and J-protein) that completely suppresses fibrilization of HttExon1Q₄₈ The composition of this chaperone complex is variable as recruitment of different chaperone family members forms distinct functional complexes. The trimeric chaperone complex is also able to resolubilize Htt fibrils. We confirmed the biological significance of these findings in HD patient-derived neural cells and on an organismal level in Caenorhabditis eleg

SUBMITTER: Scior A 

PROVIDER: S-EPMC5770855 | biostudies-literature | 2018 Jan

REPOSITORIES: biostudies-literature