黑质
多巴胺
化学
致密部
神经黑素
氧化应激
生物化学
胞浆
多巴胺能
儿茶酚胺
氧化磷酸化
生物物理学
细胞生物学
神经科学
生物
酶
作者
Enrico Monzani,Stefania Nicolis,Simone Dell’Acqua,Andrea Capucciati,Chiara Bacchella,Fabio A. Zucca,Eugene V. Mosharov,David Sulzer,Luigi Zecca,Luigi Casella
标识
DOI:10.1002/anie.201811122
摘要
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.
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