Neuroprotective effect and potential of cellular prion protein and its cleavage products for treatment of neurodegenerative disorders part I. a literature review

Introduction: The cellular prion protein (PrPC) is well known for its pathogenic roles in prion diseases, several other neurodegenerative diseases (such as Alzheimer's disease), and multiple types of cancer, but the beneficial aspects of PrPC and its cleavage products received much less attention. Areas covered: Here the authors will systematically review the literatures on the negative as well as protective aspects of PrPC and its derivatives (especially PrP N-terminal N1 peptide and shed PrP). The authors will dissect the current findings on N1 and shed PrP, including evidence for their neuroprotective effects, the categories of PrPC cleavage, and numerous cleavage enzymes involved. The authors will also discuss the protective effects and therapeutic potentials of PrPC-rich exosomes. The cited articles were obtained from extensive PubMed searches of recent literature, including peer-reviewed original articles and review articles. Expert Opinion: PrP and its N-terminal fragments have strong neuroprotective activities that should be explored for therapeutics and prophylactics development against prion disease, Alzheimer's disease and a few other neurodegenerative diseases. The strategies to develop PrP-based therapeutics and prophylactics for these neurodegenerative diseases will be discussed in a companion article (Part II).