Effects of heat shock, heat shock protein 40 (HDJ-2), and proteasome inhibition on protein aggregation in cellular models of Huntington's disease

Inhibition of mTOR induces autophagy and reduces toxicity of polyglutamine expansions in fly and mouse models of Huntington disease

“…2 online). This degree of mTOR colocalization is much greater than observed with most other proteins previously analyzed 15 . We never observed mTOR aggregation in the absence of huntingtin aggregates (data not shown).…”

Translation of HTT mRNA with expanded CAG repeats is regulated by the MID1–PP2A protein complex

“…These fragments get degraded via the ubiquitin-proteasome pathway and by autophagy. Reduction of proteasomal degradation has been found in cells carrying CAG repeat expansions [46][47][48][49] and induction of both degradation pathways has been discussed as promising therapeutic strategies for CAG repeat expansion disorders including HD [50][51][52][53] .…”

Firefly luciferase mutants as sensors of proteome stress

“…All these studies have identified genes belonging to distinct classes including genes involved in RNA metabolism (RNA pol II subunits, splicing factors), protein synthesis (ribosomes, initiation and elongation factors), protein folding (chaperones) and protein degradation (proteasome subunits and autophagy factors). The role of molecular chaperones, particularly Hsp70 and Hsp40, in suppressing Htt aggregation and its associated toxicity has been extensively elucidated using different experimental approaches (Hageman et al, 2010;Muchowski et al, 2000;Sakahira et al, 2002;Warrick et al, 1999;Wyttenbach et al, 2000). Besides molecular chaperones, cells have evolved distinct mechanisms to protect themselves from accumulation of toxic protein species.…”