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J. Biol. Chem. 276 (42): 39145-39149

© 2001 by The American Society for Biochemistry and Molecular Biology, Inc.

Prion Protein Protects Human Neurons against Bax-mediated Apoptosis*

Younes BounharDagger §, Yan ZhangDagger §, Cynthia G. Goodyer, and Andréa LeBlanc||**

From the Departments of Dagger  Neurology and Neurosurgery, and  Pediatrics, McGill University, Montréal, PQ, H3A 2T5 Canada and the || Bloomfield Center for Research in Aging, The Lady Davis Institute for Medical Research, Sir Mortimer B. Davis, Jewish General Hospital, Montreal, Quebec, H3T 1E2 Canada

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 (PrPDelta OR) 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.

* This work was supported by Grant MT-13464 from the Medical Research Council of Canada and Fonds de Recherche en Santé du Québec (to A. L. B.).The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

§ Both authors contributed equally to this work.

** To whom correspondence should be addressed: Lady Davis Inst. for Medical Research, 3755 Ch. Cote Ste-Catherine, Montreal, Quebec, H3T 1E2 Canada. Tel.: 514-340-8222, ext. 4976; Fax: 514-340-8295; E-mail: andrea.leblanc@mcgill.ca.

Copyright © 2001 by The American Society for Biochemistry and Molecular Biology, Inc.

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