Neuromelanin

Neuromelanin (NM) is a dark pigment found in the brain which is structurally related to melanin. It is a polymer of 5,6-dihydroxyindole monomers. Neuromelanin is expressed in large quantities in catecholaminergic cells of the substantia nigra pars compacta and locus coeruleus, giving dark color to the structures.

Importance in humans

Neuromelanin is found in higher concentrations among humans than in other primates. Neuromelanin-containing neurons in the substantia nigra undergo neurodegeneration during Parkinson's disease. Neuromelanin concentration increases with age, suggesting a role in neuroprotection (neuromelanin can chelate metals and xenobiotics⁺) or senescence.

Synthetic pathways

Neuromelanin is directly biosynthesized from L-DOPA, precursor to dopamine, by tyrosine hydroxylase (TH) and aromatic acid decarboxylase (AADC). Alternatively, synaptic vesicles and endosomes accumulate cytosolic dopamine (via vesicular monoamine transporter 2 (VMAT2) and transport it to mitochondria where it is metabolized by monoamine oxidase. Excess dopamine and DOPA molecules are oxidized by iron catalysis into quinones and semiquinones which are then phagocytosed and are stored as neuromelanin.