Lysosomal Enhancement Prevents Infection with PrP^Sc, α-Synuclein & Tau Prions.

ABSTRACT: Prion diseases are fatal neurodegenerative diseases of humans and other mammals with no current treatment options. Here, we describe the characterization of a novel anti-prion compound, elacridar (GW120918), which has sub-micromolar activity in assays of prion infection, propagation and toxicity. Elacridar acts at an early step in the prion infection process, enhancing degradation of newly formed PrP^Sc. The lysosome is the likely site of elacridar's anti-prion effects, based on transcriptomic analysis and the use of functional lysosomal probes. Elacridar alters gene expression networks controlling lysosomal sterol and lipid metabolism but, unlike other lysosomotropic drugs, it prominently upregulates genes that control lysosomal pH. Surprisingly, these effects occur independentl

SUBMITTER: Mercer RCC 

PROVIDER: S-EPMC12262522 | biostudies-literature | 2025 Aug

REPOSITORIES: biostudies-literature