Endoproteolysis of cellular prion protein by plasmin hinders propagation of prions.

ABSTRACT: Many questions surround the underlying mechanism for the differential metabolic processing observed for the prion protein (PrP) in healthy and prion-infected mammals. Foremost, the physiological α-cleavage of PrP interrupts a region critical for both toxicity and conversion of cellular PrP (PrP ^C ) into its misfolded pathogenic isoform (PrP ^Sc ) by generating a glycosylphosphatidylinositol (GPI)-anchored C1 fragment. During prion diseases, alternative β-cleavage of PrP becomes prominent, producing a GPI-anchored C2 fragment with this particular region intact. It remains unexplored whether physical up-regulation of α-cleavage can inhibit disease progression. Furthermore, several pieces of evidence indicate that a disintegrin and metalloproteinase (ADAM) 1

SUBMITTER: Mays CE 

PROVIDER: S-EPMC9478470 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature