Novel regulators of PrPC expression as potential therapeutic targets in prion diseases

Introduction: Prion diseases are rare and fatal neurodegenerative disorders. The key molecular event in these disorders is the misfolding of the physiological form of the cellular prion protein, PrPC, leading to the accumulation of a pathological isoform, PrPSc, with unique features. Both isoforms share the same primary sequence, lacking detectable differences in posttranslational modification, a major hurdle for their biochemical or biophysical independent characterization. The mechanism underlying the conversion of PrPC to PrPSc is not completely understood, so finding an effective therapy to cure prion disorders is extremely challenging. Areas covered: This review discusses the strategies for decreasing prion replication and throws a spotlight on the relevance of PrPC in the prion accumulation process. Expert opinion: PrPC is the key substrate for prion pathology; hence, the most promising therapeutic approach appears to be the targeting of PrPC to block the production of the infectious isoform. The use of RNA interference and antisense oligonucleotide technologies may offer opportunities for treatment because of their success in clinical trials for other neurodegenerative diseases.