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

• Published in: Acta neuropathologica Vol. 141; no. 5; pp. 725 - 754
• Main Authors: Tokarew, Jacqueline M., El-Kodsi, Daniel N., Lengacher, Nathalie A., Fehr, Travis K., Nguyen, Angela P., Shutinoski, Bojan, O’Nuallain, Brian, Jin, Ming, Khan, Jasmine M., Ng, Andy C. H., Li, Juan, Jiang, Qiubo, Zhang, Mei, Wang, Liqun, Sengupta, Rajib, Barber, Kathryn R., Tran, An, Im, Doo Soon, Callaghan, Steve, Park, David S., Zandee, Stephanie, Dong, Xiajun, Scherzer, Clemens R., Prat, Alexandre, Tsai, Eve C., Takanashi, Masashi, Hattori, Nobutaka, Chan, Jennifer A., Zecca, Luigi, West, Andrew B., Holmgren, Arne, Puente, Lawrence, Shaw, Gary S., Toth, Gergely, Woulfe, John M., Taylor, Peggy, Tomlinson, Julianna J., Schlossmacher, Michael G.
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 01.05.2021; Springer; Springer Nature B.V
• Subjects: Aging; Brain; Brain diseases; CD63 antigen; Dopamine; Dopamine receptors; Epitopes; Ethylenediaminetetraacetic acid; Free radicals (Chemistry); Hydrogen peroxide; Lysosomes; Medicin och hälsovetenskap; Medicine; Medicine & Public Health; Melanin; Mesencephalon; Metabolites; Monoclonal antibodies; Movement disorders; MPTP; Mutants; Neurodegeneration; Neurodegenerative diseases; Neurosciences; Original Paper; Oxidation; Oxidative stress; Parkin protein; Parkinson's disease; Pathology; Phenols; Redox reactions; Substantia nigra; Toxicity; Parkinsonism; Dopamine metabolism; gene; Anti-oxidant; Young-onset Parkinson disease; Redox chemistry; Neuromelanin; Parkin; PRKN/PARK2 gene

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, inc...