Taking advantage of physiological proteolytic processing of the prion protein for a therapeutic perspective in prion and Alzheimer diseases

Abstract

Prion and Alzheimer diseases are fatal neurodegenerative diseases caused by misfolding and aggregation of the cellular prion protein (PrP^C) and the β-amyloid peptide, respectively. Soluble oligomeric species rather than large aggregates are now believed to be neurotoxic. PrP^C undergoes three proteolytic cleavages as part of its natural life cycle, α-cleavage, β-cleavage, and ectodomain shedding. Recent evidences demonstrate that the resulting secreted PrP^C molecules might represent natural inhibitors against soluble toxic species. In this mini-review, we summarize recent observations suggesting the potential benefit of using PrP^C-derived molecules as therapeutic agents in prion and Alzheimer diseases.

Keywords: :

• Alzheimer disease
• PrPN1
• neuroprotection
• prion
• prion disease
• shedding
• α-cleavage
• β-cleavage

10.4161/pri.27438

Disclosure of Potential Conflicts of Interest

No potential conflicts of interest were disclosed.

Acknowledgments

This research was supported in part by a grant from the Fonds de Recherche en Santé, Québec and the Canadian Institutes for Health Research (MOP-89881) to X.R. We thank Julie Motard and Guillaume Tremblay for critical reading of the manuscript.