Compounds blocking mutant huntingtin toxicity identified using a Huntington's disease neuronal cell model.

摘要: Neuronal cell death in HD is believed to be largely a dominant cell-autonomous effect of the mutant huntingtin protein. We previously developed an inducible PC12 model which expresses N-terminal fragment with expanded poly Q repeat (N63-148Q) under control tet-off system. In order evaluate ability compounds protect against toxicity our model, we measured LDH released by dead cells into medium. have now screened library 1040 from NINDS Custom Collection as part National Institute Neurological Disorders and Stroke (NINDS) collaborative project. Each positive compound was tested at 3-8 concentrations. Five significantly attenuated (htt)-induced release without affecting expression level independent on aggregates. also broad spectrum caspase inhibitor Z-VAD-fmk proposed candidate compounds. This can provide method screen potential therapeutic for treating Huntington's disease.