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.
Physical properties and structure
Neuromelanin gives specific brain sections, such as the substantia nigra or the locus coeruleus, distinct color. It is a type of melanin and similar to other forms of peripheral melanin. It is insoluble in organic compounds, and can be labeled by
silver staining. It is called neuromelanin because of its function and the color change that appears in tissues containing it. It contains black/brown pigmented granules. Neuromelanin is found to accumulate during aging, noticeably after the
toddler of life. It is believed to protect neurons in the substantia nigra from iron-induced oxidative stress. It is considered a true melanin due to its stable
free radical structure and it avidly
Chelation metals.
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
Catalysis into
L-Dopaquinone and
Semiquinone which are then
Phagocytosis and are stored as neuromelanin.
Neuromelanin biosynthesis is driven by excess cytosolic catecholamines not accumulated by synaptic vesicles.
Function
Neuromelanin is found in higher concentrations in humans than in other
.
Neuromelanin concentration increases with age, suggesting a role in
neuroprotection (neuromelanin can
chelate metals and
) or
senescence.
Role in disease
Neuromelanin-containing
in the substantia nigra degenerate during Parkinson's disease. Motor symptoms of Parkinson's disease are caused by cell death in the substantia nigra, which may be partly due to
oxidative stress. This oxidation may be relieved by neuromelanin. Patients with Parkinson's disease had 50% the amount of neuromelanin in the substantia nigra as compared to similar patients of their same age, but without Parkinson's. The death of neuromelanin-containing neurons in the substantia nigra,
pars compacta, and locus coeruleus have been linked to Parkinson's disease and also have been visualized
in vivo with neuromelanin imaging.
Neuromelanin has been shown to bind neurotoxic and toxic metals that could promote neurodegeneration.
History
Dark pigments in the substantia nigra were first described in 1838 by Purkyně,
and the term neuromelanin was proposed in 1957 by Lillie,
though it has been thought to serve no function until recently. It is now believed to play a vital role in preventing cell death in certain parts of the brain. It has been linked to Parkinson's disease and because of this possible connection, neuromelanin has been heavily researched in the last decade.
