Structural and Functional Characterization of the Most Frequent Pathogenic PRKN Substitution p.R275W.

ABSTRACT: Mutations in the PINK1 and PRKN genes are the most frequent genetic cause of early-onset Parkinson disease. The pathogenic p.R275W substitution in PRKN is the most frequent substitution observed in patients, and thus far has been characterized mostly through overexpression models that suggest a possible gain of toxic misfunction. However, its effects under endogenous conditions are largely unknown. We used patient fibroblasts, isogenic neurons, and post-mortem human brain samples from carriers with and without PRKN p.R275W to assess functional impact. Immunoblot analysis and immunofluorescence were used to study mitophagy activation, and mitophagy execution was analyzed by flow cytometry of the reporter mitoKeima. The functional analysis was accompanied by structural investig

SUBMITTER: Bustillos BA 

PROVIDER: S-EPMC11430725 | biostudies-literature | 2024 Sep

REPOSITORIES: biostudies-literature