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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 Bounhar{ddagger}§, Yan Zhang{ddagger}§, Cynthia G. Goodyer, , and Andréa LeBlanc||**

From the Departments of {ddagger}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

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Abstract: 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 (PrP{Delta}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.

Received for publication August 7, 2001. Revision received August 23, 2001.

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Expression of truncated PrP targeted to Purkinje cells of PrP knockout mice causes Purkinje cell death and ataxia.
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   Abstract »    Full Text »    PDF »
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   Abstract »    Full Text »    PDF »
The PrP-like Protein Doppel Binds Copper.
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   Abstract »    Full Text »    PDF »
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Cellular prion protein transduces neuroprotective signals.
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Selective cytotoxicity of intracellular amyloid {beta} peptide1-42 through p53 and Bax in cultured primary human neurons.
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J. Cell Biol. 156, 519-529
   Abstract »    Full Text »    PDF »
Selective cytotoxicity of intracellular amyloid {beta} peptide1-42 through p53 and Bax in cultured primary human neurons.
Y. Zhang, R. McLaughlin, C. Goodyer, and A. LeBlanc (2002)
J. Cell Biol. 156, 519-529
   Abstract »    Full Text »    PDF »

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