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 (PrPC) and the ?-amyloid peptide, respectively. Soluble oligomeric species rather than large aggregates are now believed to be neurotoxic. PrPC 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 PrPC molecules might represent natural inhibitors against soluble toxic species. In this mini-review, we summarize recent observations suggesting the potential benefit of using PrPC-derived molecules as therapeutic agents in prion and Alzheimer diseases. © 2014 Landes Bioscience.