Chaperone-mediated disaggregation of infectious prions releases particles that seed new prion formation in a strain-specific manner.

ABSTRACT: The mammalian prion protein can form infectious, nonnative, and protease resistant aggregates (PrP^D), which cause lethal prion diseases like human Creutzfeldt-Jakob disease. PrP^D seeds the formation of new infectious prions by interacting with and triggering the refolding of the normally soluble mammalian prion protein, PrP^C, into more PrP^D. Refolding of misfolded proteins in the cell is carried out by molecular chaperones such as Grp78. We have recently shown that Grp78 sensitizes PrP^D to proteases, indicating structural alterations and leading to its degradation. However, the process of chaperone-mediated PrP^D disaggregation, the chaperones involved, and the effect of disaggregation on PrP^D seeding activity are

SUBMITTER: Shoup D 

PROVIDER: S-EPMC11758957 | biostudies-literature | 2025 Jan

REPOSITORIES: biostudies-literature