title: New melanic pigments in the human brain that accumulate in aging and block environmental toxic metals.
abstract: 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.
authors.affiliation: Institute of Biomedical Technologies, Italian National Research Council, 20090 Segrate, Milan, Italy. luigi.zecca@itb.cnr.it
authors.forename: Luigi
authors.initials: L
authors.lastname: Zecca
authors.forename: Chiara
authors.initials: C
authors.lastname: Bellei
authors.forename: Patrizia
authors.initials: P
authors.lastname: Costi
authors.forename: Alberto
authors.initials: A
authors.lastname: Albertini
authors.forename: Enrico
authors.initials: E
authors.lastname: Monzani
authors.forename: Luigi
authors.initials: L
authors.lastname: Casella
authors.forename: Mario
authors.initials: M
authors.lastname: Gallorini
authors.forename: Luigi
authors.initials: L
authors.lastname: Bergamaschi
authors.forename: Alberto
authors.initials: A
authors.lastname: Moscatelli
authors.forename: Nicholas J
authors.initials: NJ
authors.lastname: Turro
authors.forename: Melvin
authors.initials: M
authors.lastname: Eisner
authors.forename: Pier Raimondo
authors.initials: PR
authors.lastname: Crippa
authors.forename: Shosuke
authors.initials: S
authors.lastname: Ito
authors.forename: Kazumasa
authors.initials: K
authors.lastname: Wakamatsu
authors.forename: William D
authors.initials: WD
authors.lastname: Bush
authors.forename: Weslyn C
authors.initials: WC
authors.lastname: Ward
authors.forename: John D
authors.initials: JD
authors.lastname: Simon
authors.forename: Fabio A
authors.initials: FA
authors.lastname: Zucca
mesh_terms: 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*
chemical_list: D004785:Environmental Pollutants; D008543:Melanins; D019216:Metals, Heavy; C014121:neuromelanin