Age-associated insolubility of parkin in human midbrain is linked to redox balance and sequestration of reactive dopamine metabolites.

ABSTRACT: The mechanisms by which parkin protects the adult human brain from Parkinson disease remain incompletely understood. We hypothesized that parkin cysteines participate in redox reactions and that these are reflected in its posttranslational modifications. We found that in post mortem human brain, including in the Substantia nigra, parkin is largely insoluble after age 40 years; this transition is linked to its oxidation, such as at residues Cys95 and Cys253. In mice, oxidative stress induces posttranslational modifications of parkin cysteines that lower its solubility in vivo. Similarly, oxidation of recombinant parkin by hydrogen peroxide (H₂O₂) promotes its insolubility and aggregate formation, and in exchange leads to the reduction of H₂O₂. Thi

SUBMITTER: Tokarew JM 

PROVIDER: S-EPMC8043881 | biostudies-literature | 2021 May

REPOSITORIES: biostudies-literature