Prion Protein Protects Human Neurons against Bax-mediated Apoptosis

作者：Younes Bounhar, Yan Zhang, Cynthia Gates Goodyer, Andrea Claire LeBlanc · 发表于：Journal of Biological Chemistry · 年份：2001 · DOI：10.1074/jbc.c100443200 · 被引用次数：381 · 研究领域：Prion Diseases and Protein Misfolding、RNA regulation and disease、Trace Elements in Health

The function of the cellular prion protein (PrP) is still poorly understood. We present here an unprecedented role for PrP against Bax-mediated neuronal apoptosis and show that PrP potently inhibits Bax-induced cell death in human primary neurons. Deletion of four octapeptide repeats of PrP (PrPDeltaOR) and familial D178N and T183A PrP mutations completely or partially eliminate the neuroprotective effect of PrP. PrP remains anti-apoptotic despite truncation of the glycosylphosphatidylinositol (GPI) anchor signal peptide, indicating that the neuroprotective form of PrP does not require the abundant cell surface GPI-anchored PrP. Our results implicate PrP as a potent and novel anti-apoptotic protein against Bax-mediated cell death.