[HTML][HTML] Inhibition of calpain cleavage of huntingtin reduces toxicity: accumulation of calpain/caspase fragments in the nucleus
J Gafni, E Hermel, JE Young, CL Wellington… - Journal of Biological …, 2004 - ASBMB
Huntington's disease (HD) is a neurodegenerative disorder caused by a polyglutamine
(polyQ) tract expansion near the N terminus of huntingtin (Htt). Proteolytic processing of
mutant Htt and abnormal calcium signaling may play a critical role in disease progression
and pathogenesis. Recent work indicates that calpains may participate in the increased
and/or altered patterns of Htt proteolysis leading to the selective toxicity observed in HD
striatum. Here, we identify two calpain cleavage sites in Htt and show that mutation of these …
(polyQ) tract expansion near the N terminus of huntingtin (Htt). Proteolytic processing of
mutant Htt and abnormal calcium signaling may play a critical role in disease progression
and pathogenesis. Recent work indicates that calpains may participate in the increased
and/or altered patterns of Htt proteolysis leading to the selective toxicity observed in HD
striatum. Here, we identify two calpain cleavage sites in Htt and show that mutation of these …