Oligosaccharyltransferase (OST) complex inhibition effectively treats rodent and human prions.

ABSTRACT: Prion diseases are invariably fatal neurodegenerative diseases that occur when the prion protein misfolds into a pathogenic form. There are currently no clinical treatments or cures for prion disease. Current challenges in the development of prion therapeutics include prion strain specificity, which can cause the emergence of drug-resistant prions, and lack of efficacy in treating human prions despite promising results in rodent models. Here we identify a novel therapeutic target for prion disease: the oligosaccharyltransferase (OST) complex. The OST complex is responsible for transferring the mature glycan to the acceptor polypeptide during N-glycosylation. We found that inhibiting OST effectively treats rodent prions in various dividing and non-dividing cell types. Importantly, we also d

SUBMITTER: Beauchemin KS 

PROVIDER: S-EPMC12818742 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature