Neuromelanins in brain aging and Parkinson's disease: synthesis, structure, neuroinflammatory, and neurodegenerative role.

Neuromelanins are compounds accumulating in neurons of human and animal brain during aging, with neurons of substantia nigra and locus coeruleus having the highest levels of neuromelanins. These compounds have melanic, lipid, peptide, and inorganic components and are contained inside special autolysosomes. Neuromelanins can participate in neuroprotective or toxic processes occurring in Parkinson's disease according to cellular environment.

Neuromelanin-sensitive MRI as a noninvasive proxy measure of dopamine function in the human brain.

Neuromelanin-sensitive MRI (NM-MRI) purports to detect the content of neuromelanin (NM), a product of dopamine metabolism that accumulates with age in dopamine neurons of the substantia nigra (SN). Interindividual variability in dopamine function may result in varying levels of NM accumulation in the SN; however, the ability of NM-MRI to measure dopamine function in nonneurodegenerative conditions has not been established. Here, we validated that NM-MRI signal intensity in postmortem midbrain specimens correlated with regional NM concentration even in the absence of neurodegeneration, a prerequisite for its use as a proxy for dopamine function.

Neuromelanin organelles are specialized autolysosomes that accumulate undegraded proteins and lipids in aging human brain and are likely involved in Parkinson's disease.

During aging, neuronal organelles filled with neuromelanin (a dark-brown pigment) and lipid bodies accumulate in the brain, particularly in the substantia nigra, a region targeted in Parkinson's disease. We have investigated protein and lipid systems involved in the formation of these organelles and in the synthesis of the neuromelanin of human substantia nigra. Membrane and matrix proteins characteristic of lysosomes were found in neuromelanin-containing organelles at a lower number than in typical lysosomes, indicating a reduced enzymatic activity and likely impaired capacity for lysosomal and autophagosomal fusion.

Neuromelanins of human brain have soluble and insoluble components with dolichols attached to the melanic structure.

Neuromelanins (NMs) are neuronal pigments of melanic-lipidic type which accumulate during aging. They are involved in protective and degenerative mechanisms depending on the cellular context, however their structures are still poorly understood. NMs from nine human brain areas were analyzed in detail.

Neuromelanins in various regions of human brain are associated with native and oxidized isoprenoid lipids.

Neuromelanin (NM) isolated from seven regions of the human brain is found to contain series of natural and oxidized isoprenoid lipids. Specifically, dolichols (dol) and dolichoic acids (dol-CA) with 14-22 and 14-21 isoprene units are identified. Standards of nor-dolichol and nor-dolichoic acid were used to determine the relative amounts of dol and dol-CA compared to the total lipids present in NM for each region.

Neuromelanins isolated from different regions of the human brain exhibit a common surface photoionization threshold.

Neuromelanin isolated from the premotor cortex, cerebellum, putamen, globus pallidus and corpus callosum of the human brain is studied by scanning probe and photoelectron emission microscopies and the results are compared with previously published work on neuromelanin from the substantia nigra. Scanning electron microscopy reveals common structure for all neuromelanins. All exhibit spherical entities of diameters between 200 and 400 nm, composed of smaller spherical substructures, approximately 30 nm in diameter.

New melanic pigments in the human brain that accumulate in aging and block environmental toxic metals.

Neuronal pigments of melanic type were identified in the putamen, cortex, cerebellum, and other major regions of human brain. These pigments consist of granules 30 nm in size, contained in organelles together with lipid droplets, and they accumulate in aging, reaching concentrations as high as 1.5-2.

Neuromelanin can protect against iron-mediated oxidative damage in system modeling iron overload of brain aging and Parkinson's disease.

In Parkinson's disease (PD), dopamine neurons containing neuromelanin selectively degenerate. Neuromelanin binds iron and accumulates in aging. Iron accumulates in reactive form during aging, PD, and is involved in neurodegeneration.