Model of polyglutamine induced toxicity.

<p>Activation p38MAPK signaling is counteracted by PKCι-mediated ERK activation in expanded polyglutamine expressing cells. The pharmacological blockade of ERK with U0126 or by PKCι depletion sensitizes cells to polyglutamine-induced death through a mechanism of exaggerated induction of p38MAPK (A). In contrast, inhibition of p38MAPK phosphorylation by SKF86002 or SB202190 rescues cells from polyglutamine toxicity (B). The blockade of both signaling pathways in cells expressing expanded polyglutamine proteins recapitulates blockade of p38MAPK (B) indicating a causative association between p38MAPK induction and polyglutamine induced death.