Neuromelanin detection by magnetic resonance imaging (MRI) and its promise as a biomarker for Parkinson’s disease

Mechanisms for biosynthesis of NM pigment and for the formation of NM-containing organelles in human SN. Excess dopamine in the cytosol of SN neurons can be oxidized to quinones by ferric iron. These highly reactive compounds can bind to aggregated and β-structured proteins that accumulate in the cytosol. An oxidative polymerization initiates formation of the melanin-protein component with eumelanin and pheomelanin moieties that can also bind high amounts of metals, particularly iron. Via macroautophagy, the resulting undegradable material is taken into autophagic vacuoles that fuse with lysosomes and other autophagic vacuoles containing lipid and protein components, thus forming the final NM-containing organelles that contain NM pigment along with metals, abundant lipid bodies, and protein matrix. The process continues during the life of the neuron, so that SN dopamine neurons accumulate high numbers of NM-containing organelles with age. This scheme is based on characterizations by multiple techniques of lipid and protein systems in NM-containing organelles of the human SN (Zucca et al., under review). Figure modified from ref. 20 by permission of Springer and ref. 21 by permission of Elsevie