Necrostatin-1 ameliorates symptoms in R6/2 transgenic mouse model of Huntington's disease

S Zhu,H Li,Y Zhang,G Bai

doi:10.1038/cddis.2010.94

Abstract

Necrostatin-1 ameliorates symptoms in R6/2 transgenic mouse model of Huntington's disease

Highlights

ST14A is an immortalized striatal cell line with medium spiny neurons (MSNs) characteristics[6] and ST14A 8plx line stably expressing mutant Htt fragment (N548-128Q) was established as a cell model of Huntington’s disease (HD).[7,8] To our surprise, pan-caspases inhibitor zVAD-fmk efficiently induced ST14A 8plx cell to death, which can be almost completely rescued by Nec-1 (Figures 1a and b)
Further experiments with selective caspase inhibitors revealed that caspase-8 inhibitor (IETD-fmk), but not caspase-3 (DEVD-fmk) or caspase-9 (LEHD-fmk) inhibitor, had the similar necroptosis-inducing effect as zVAD-fmk (Figures 1a and b and Supplementary Figure S1b)
We noticed that there were more full-length RIP1 proteins in 8plx cells compared with parental cells (Supplementary Figure S1e)

Summary

Introduction

ST14A is an immortalized striatal cell line with MSNs characteristics[6] and ST14A 8plx line stably expressing mutant Htt fragment (N548-128Q) was established as a cell model of HD.[7,8] To our surprise, pan-caspases inhibitor zVAD-fmk efficiently induced ST14A 8plx cell to death, which can be almost completely rescued by Nec-1 (Figures 1a and b). Necrostatin-5 did not inhibit zVAD-fmk-induced striatal cell death (data not shown).

Results

Conclusion