Huntington's disease (HD) is caused by a polyglutamine expansion in the amino-terminal
region of huntingtin. Mutant huntingtin is proteolytically cleaved by caspases, generating
amino-terminal aggregates that are toxic for cells. The addition of calpains to total brain
homogenates also leads to cleavage of wild-type huntingtin, indicating that proteolysis of
mutant and wild-type huntingtin may play a role in HD. Here we report that endogenous wild-
type huntingtin is promptly cleaved by calpains in primary neurons. Exposure of primary …