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Dopamine, Oxidative Stress and Protein–Quinone Modifications in Parkinson's and Other Neurodegenerative Diseases
Author(s) -
Monzani Enrico,
Nicolis Stefania,
Dell'Acqua Simone,
Capucciati Andrea,
Bacchella Chiara,
Zucca Fabio A.,
Mosharov Eugene V.,
Sulzer David,
Zecca Luigi,
Casella Luigi
Publication year - 2019
Publication title -
angewandte chemie international edition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.831
H-Index - 550
eISSN - 1521-3773
pISSN - 1433-7851
DOI - 10.1002/anie.201811122
Subject(s) - substantia nigra , dopamine , pars compacta , chemistry , neuromelanin , oxidative stress , cytosol , biochemistry , catecholamine , oxidative phosphorylation , biophysics , microbiology and biotechnology , neuroscience , biology , enzyme , dopaminergic
Abstract Dopamine (DA) is the most important catecholamine in the brain, as it is the most abundant and the precursor of other neurotransmitters. Degeneration of nigrostriatal neurons of substantia nigra pars compacta in Parkinson's disease represents the best‐studied link between DA neurotransmission and neuropathology. Catecholamines are reactive molecules that are handled through complex control and transport systems. Under normal conditions, small amounts of cytosolic DA are converted to neuromelanin in a stepwise process involving melanization of peptides and proteins. However, excessive cytosolic or extraneuronal DA can give rise to nonselective protein modifications. These reactions involve DA oxidation to quinone species and depend on the presence of redox‐active transition metal ions such as iron and copper. Other oxidized DA metabolites likely participate in post‐translational protein modification. Thus, protein–quinone modification is a heterogeneous process involving multiple DA‐derived residues that produce structural and conformational changes of proteins and can lead to aggregation and inactivation of the modified proteins.