GRP78 counteracts cell death and protein aggregation caused by mutant huntingtin proteins.

The ER-localized chaperone glucose-regulated protein (GRP78) protects neurons against excitotoxicity and apoptosis. Here we show that overexpressing GRP78 protects N2a cells against mutant huntingtin proteins, reduces formation of mutant huntingtin aggregates, inhibits caspase-12 activation and blocks cell death. Our data suggest that GRP78 may be a promising therapeutic target for the treatment of Huntington's disease.