Syntaxin-6 delays prion protein fibril formation and prolongs the presence of toxic aggregation intermediates.

ABSTRACT: Prions replicate via the autocatalytic conversion of cellular prion protein (PrP^C) into fibrillar assemblies of misfolded PrP. While this process has been extensively studied in vivo and in vitro, non-physiological reaction conditions of fibril formation in vitro have precluded the identification and mechanistic analysis of cellular proteins, which may alter PrP self-assembly and prion replication. Here, we have developed a fibril formation assay for recombinant murine and human PrP (23-231) under near-native conditions (NAA) to study the effect of cellular proteins, which may be risk factors or potential therapeutic targets in prion disease. Genetic screening suggests that variants that increase syntaxin-6 expression in the brain (gene: STX6) are risk factors for sporadic Creut

SUBMITTER: Sangar D 

PROVIDER: S-EPMC11377041 | biostudies-literature | 2024 Aug

REPOSITORIES: biostudies-literature