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. For these reasons, protein dopamination is difficult to recognize and characterize, although recent advancements have been made through in vitro studies. Neuromelanin itself is a heterogeneous, insoluble substance containing a large number of proteins covalently modified by melanic and lipidic components. Better knowledge of protein-quinone modifications and neuromelanin biosynthetic pathways will improve our understanding of brain disorders linked to catecholamine toxicity and provide an important background for the interpretation of magnetic resonance imaging signatures of neuromelanin as a tool for early diagnosing Parkinson’s disease.

Dopamine, oxidative stress and protein-quinone modifications in Parkinson's and other neurodegenerative diseases

E. Monzani
;
S. Nicolis;S. Dell'Acqua;CAPUCCIATI, ANDREA;BACCHELLA, CHIARA;L. Casella
2019-01-01

Abstract

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. For these reasons, protein dopamination is difficult to recognize and characterize, although recent advancements have been made through in vitro studies. Neuromelanin itself is a heterogeneous, insoluble substance containing a large number of proteins covalently modified by melanic and lipidic components. Better knowledge of protein-quinone modifications and neuromelanin biosynthetic pathways will improve our understanding of brain disorders linked to catecholamine toxicity and provide an important background for the interpretation of magnetic resonance imaging signatures of neuromelanin as a tool for early diagnosing Parkinson’s disease.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11571/1242586
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