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 1.5-2.6 microg/mg tissue in major brain regions. These pigments, which we term neuromelanins, contain melanic, lipid, and peptide components. The melanic component is aromatic in structure, contains a stable free radical, and is synthesized from the precursor molecule cysteinyl-3,4-dihydroxyphenylalanine. This contrasts with neuromelanin of the substantia nigra, where the melanic precursor is cysteinyl-dopamine. These neuronal pigments have some structural similarities to the melanin found in skin. The precursors of lipid components of the neuromelanins are the polyunsaturated lipids present in the surrounding organelles. The synthesis of neuromelanins in the various regions of the human brain is an important protective process because the melanic component is generated through the removal of reactive/toxic quinones that would otherwise cause neurotoxicity. Furthermore, the resulting melanic component serves an additional protective role through its ability to chelate and accumulate metals, including environmentally toxic metals such as mercury and lead.
Zecca
Luigi
L
Institute of Biomedical Technologies, Italian National Research Council, 20090 Segrate, Milan, Italy. luigi.zecca@itb.cnr.it
Bellei
Chiara
C
Costi
Patrizia
P
Albertini
Alberto
A
Monzani
Enrico
E
Casella
Luigi
L
Gallorini
Mario
M
Bergamaschi
Luigi
L
Moscatelli
Alberto
A
Turro
Nicholas J
NJ
Eisner
Melvin
M
Crippa
Pier Raimondo
PR
Ito
Shosuke
S
Wakamatsu
Kazumasa
K
Bush
William D
WD
Ward
Weslyn C
WC
Simon
John D
JD
Zucca
Fabio A
FA
D000375:Aging / Q000378:metabolism*; D001921:Brain / Q000378:metabolism* / Q000648:ultrastructure; D004785:Environmental Pollutants / Q000378:metabolism*; D006801:Humans; D008543:Melanins / Q000096:biosynthesis* / Q000737:chemistry; D019216:Metals, Heavy / Q000378:metabolism*; D008854:Microscopy, Electron; D009474:Neurons / Q000737:chemistry* / Q000166:cytology; D015388:Organelles / Q000737:chemistry*
D004785:Environmental Pollutants; D008543:Melanins; D019216:Metals, Heavy; C014121:neuromelanin