Cited by 240Parkinson's Disease Mechanisms and Treatmentsmelanin and skin pigmentationHeavy Metal Exposure and Toxicity

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

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Zecca, Luigi, Bellei, Chiara, Costi, Patrizia, Albertini, Alberto, Monzani, Enrico, Casella, Luigi, Gallorini, Mario, Bergamaschi, Luigi, Moscatelli, Alberto, Turro, Nicholas J., Eisner, Melvin, Crippa, Pier Raimondo, Ito, Shosuke, Wakamatsu, Kazumasa, Bush, William D., Ward, Weslyn C., Simon, John D., Zucca, Fabio A.·2008·Proceedings of the National Academy of Sciences

DOI 10.1073/pnas.0808768105PMC PMC2582310

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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.

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Authors: Zecca, L., Bellei, C., Costi, P., Albertini, A., Monzani, E., Casella, L., Gallorini, M., Bergamaschi, L., Moscatelli, A., Turro, N. J., Eisner, M., Crippa, P. R., Ito, S., Wakamatsu, K., Bush, W. D., Ward, W. C., Simon, J. D., & Zucca, F. A.
Affiliations: Institute of Biomedical Technologies (IT)
University of Pavia (IT)
National Institute of Metrology, Unit of Radiochemistry and Spectroscopy, 27100 Pavia, Italy;
Columbia University (US)
University of Houston (US)
University of Parma (IT)
Fujita Health University (JP)
Duke University (US)
ORCID: Zecca, Luigi
Albertini, Alberto
Monzani, Enrico
Casella, Luigi
Bergamaschi, Luigi
Ito, Shosuke
Wakamatsu, Kazumasa
Zucca, Fabio A.
Venue: Proceedings of the National Academy of Sciences
Publisher: National Academy of Sciences
Published: 2008-11-11
Volume: 105
Issue: 45
Pages: 17567-17572
ISSN: 0027-8424 (ISSN-L)
1091-6490
DOI: 10.1073/pnas.0808768105
PMC: PMC2582310
OpenAlex: W2137504359
Cited by: 240
References: 31
Citations by year: 2026: 9 · 2025: 17 · 2024: 10 · 2023: 24 · 2022: 21 · 2021: 19 · 2020: 21 · 2019: 18 · 2018: 17 · 2017: 11 · 2016: 11 · 2015: 12 · 2014: 12 · 2013: 7 · 2012: 8
FWCI: 4.89
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Locations: Proceedings of the National Academy of Sciences (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
CINECA IRIS Institutional Research Information System (IRIS Istituto Nazionale di Ricerca Metrologica) (submittedVersion)
Funders: National Science Foundation
Ministero dell’Istruzione, dell’Università e della Ricerca (RBNE03PX83)
Japan Society for the Promotion of Science (19500332)
Division of Chemistry (CHE 07 17518)
Air Force Office of Scientific Research
Topics: Health Sciences › Medicine › Clinical Neurology › Parkinson's Disease Mechanisms and Treatments
Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › melanin and skin pigmentation
Physical Sciences › Environmental Science › Health, Toxicology and Mutagenesis › Heavy Metal Exposure and Toxicity
Keywords: neuromelanin, human brain, brain aging, putamen, substantia nigra, lipid droplets, free radicals, polyunsaturated lipids, metal chelation, mercury, lead, neuroprotection, quinone detoxification
MeSH terms: Aging, Brain, Environmental Pollutants, Humans, Melanins, Microscopy, Electron, Neurons, Organelles, Metals, Heavy

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

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