Recombinant ovine prion protein can be mutated at position 136 to improve its efficacy as an inhibitor of prion propagation.

ABSTRACT: Prion diseases are progressive neurodegenerative disorders with no effective therapeutics. The central event leading to the pathology in the diseases is the conversion of PrP^C into PrP^Sc and its accumulation in the central nervous system. Previous studies demonstrated that recombinant PrP (rPrP) and PrP peptides can inhibit the formation of PrP^Sc. Here, the effectiveness of ovine rPrP mutants at codon 136 and peptides derived from this region were assessed for their ability to inhibit PrP^Sc replication, using protein misfolding cyclic amplification (PMCA). Based on a rPrP VRQ (rVRQ) genotype background (positions 136, 154 and 171) and mutations at position 136, the most effective inhibitors were V136R, V136K and V136P mutants, with IC50 values of

SUBMITTER: Kopycka K 

PROVIDER: S-EPMC9978027 | biostudies-literature | 2023 Mar

REPOSITORIES: biostudies-literature