Intracellular trafficking SNARE protein, syntaxin-6, modifies prion cellular phenotypes and risk of disease development in vivo.

ABSTRACT: Increased expression of syntaxin-6, a SNARE protein involved in intracellular protein trafficking, is a proposed genetic risk mechanism for sporadic prion disease and progressive supranuclear palsy, as well as being implicated in Alzheimer's disease. However, no study has validated its functional role in prion disease, its mechanism of action nor explored the disease stage at which it is acting. Here, we show that syntaxin-6 knockdown in cellular models increases cell-associated infectivity, whilst overexpression produces the opposite effect. This observation is broadly consistent across multiple cell types and prion strains. Furthermore, syntaxin-6 knockdown leads to an accumulation of perinuclear disease-related PrP, consistent with a trafficking mechanism, and alters the morphology of d

SUBMITTER: Hill E 

PROVIDER: S-EPMC12586215 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature