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

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.