Beta-endoproteolysis of the cellular prion protein by dipeptidyl peptidase-4 and fibroblast activation protein.

ABSTRACT: The cellular prion protein (PrP^C) converts to alternatively folded pathogenic conformations (PrP^Sc) in prion infections and binds neurotoxic oligomers formed by amyloid-β α-synuclein, and tau. β-Endoproteolysis, which splits PrP^C into N- and C-terminal fragments (N2 and C2, respectively), is of interest because a protease-resistant, C2-sized fragment (C2^Sc) accumulates in the brain during prion infections, seemingly comprising the majority of PrP^Sc at disease endpoint in mice. However, candidates for the underlying proteolytic mechanism(s) remain unconfirmed in vivo. Here, a cell-based screen of protease inhibitors unexpectedly linked type II membrane proteins of the S9B serine peptidase subfamily to PrP^C β-cleavage. Overexp

SUBMITTER: Castle AR 

PROVIDER: S-EPMC9910601 | biostudies-literature | 2023 Jan

REPOSITORIES: biostudies-literature