Introduction:The cellular prion protein (PrP C ), some of its derivatives (especially PrP N-terminal N1 peptide and shed PrP), and PrP C -containing exosomes have strong neuroprotective activities, which have been reviewed in the companion article (Part I) and are briefly summarized here. Areas covered: We propose that elevating the extracellular levels of a protective PrP form using gene therapy and other approaches is a very promising novel avenue for prophylactic and therapeutic treatments against prion disease, Alzheimer's disease, and several other neurodegenerative diseases. We will dissect the pros and cons of various potential PrP-based treatment options and propose a few strategies that are more likely to succeed. The cited references were obtained from extensive PubMed searches of recent literature, including peer-reviewed original articles and review articles. Expert opinion: Concurrent knockdown of celllular PrP expression and elevation of the extracellular levels of a neuroprotective PrP N-terminal peptide via optimized gene therapy vectors is a highly promising broad-spectrum prophylactic and therapeutic strategy against several neurodegenerative diseases, including prion diseases, Alzheimer's disease and Parkinson's disease.
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