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

The DOI matches its Crossref record; 31 of the 31 references it cites were found in a registry or an index.

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

Open access

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

Open this paper in CoChat — free account

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.

Integrity signals

Registry

Crossref · 10.1073/pnas.0808768105

Cites

31 of 31 references verified0 citation errors · 0 not checkable

Statistics

Recomputing p-values needs the paper’s full text.

Claims the paper makes

We couldn’t retrieve this paper’s full text, so its claims and self-check weren’t run. The registry and citation checks still apply.

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Functional amyloid – from bacteria to humans
Fowler, D. M., Koulov, A. V., Balch, W. E., & Kelly, J. W. (2007) · Trends in Biochemical Sciences · doi:10.1016/j.tibs.2007.03.003 · Cited by 1,052
Role of oxidation in the neurotoxic effects of intrastriatal dopamine injections.
Hastings, T. G., Lewis, D. A., & Zigmond, M. J. (1996) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.93.5.1956 · Cited by 547
The role of iron and copper molecules in the neuronal vulnerability of locus coeruleus and substantia nigra during aging
Zecca, L., Stroppolo, A., Gatti, A., Tampellini, D., Toscani, M., Gallorini, M., Giaveri, G., Arosio, P., Santambrogio, P., Fariello, R. G., et al. (2004) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0403495101 · Cited by 495
Structures for amyloid fibrils
Makin, O. S., & Serpell, L. C. (2005) · FEBS Journal · doi:10.1111/j.1742-4658.2005.05025.x · Cited by 475
Neuromelanin biosynthesis is driven by excess cytosolic catecholamines not accumulated by synaptic vesicles
Sulzer, D. L., Bogulavsky, J. J., Larsen, K. E., Behr, G. G., Karatekin, E., Kleinman, M. H., Turro, N. J., Krantz, D. E., Edwards, R. H., Greene, L. A., et al. (2000) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.97.22.11869 · Cited by 460
Selectivity of the Parkinsonian Neurotoxin MPTP: Toxic Metabolite MPP + Binds to Neuromelanin
D’Amato, R. J., Lipman, Z. P., & Snyder, S. H. (1986) · Science · doi:10.1126/science.3080808 · Cited by 296
The absolute concentration of nigral neuromelanin, assayed by a new sensitive method, increases throughout the life and is dramatically decreased in Parkinson's disease
Zecca, L., Fariello, R. G., Riederer, P. F., Sulzer, D. L., Gatti, A., & Tampellini, D. (2001) · FEBS Letters · doi:10.1016/s0014-5793(01)03269-0 · Cited by 287
Aspects on human amyloid forms and their fibril polypeptides
Westermark, P. (2005) · FEBS Journal · doi:10.1111/j.1742-4658.2005.05024.x · Cited by 253
Dopaminergic Neurons Intrinsic to the Primate Striatum
Betarbet, R. S., Turner, R. S., Chockkan, V., DeLong, M. R., Allers, K. A., Walters, J. R., Levey, A. I., & Greenamyre, J. T. (1997) · Journal of Neuroscience · doi:10.1523/jneurosci.17-17-06761.1997 · Cited by 251
Is the Vulnerability of Neurons in the Substantia Nigra of Patients with Parkinson's Disease Related to Their Neuromelanin Content?
Kästner, A., Hirsch, É. C., Lejeune, O., Javoy-Agid, F., Rascol, O., & Agid, Y. (1992) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.1992.tb08350.x · Cited by 228

Flagged first, then by citations

Show all 31 references

Sorted by citations

The role of iron in brain ageing and neurodegenerative disorders
Ward, R. J., Zucca, F. A., Duyn, J. H., Crichton, R. R., & Zecca, L. (2014) · The Lancet Neurology · doi:10.1016/s1474-4422(14)70117-6 · Cited by 1,819
Dopamine oxidation mediates mitochondrial and lysosomal dysfunction in Parkinson’s disease
Burbulla, L. F., Song, P., Mazzulli, J. R., Zampese, E., Wong, Y. C., Jeon, S., Santos, D. P., Blanz, J., Obermaier, C. D., Strojny, C., et al. (2017) · Science · doi:10.1126/science.aam9080 · Cited by 874
Interactions of iron, dopamine and neuromelanin pathways in brain aging and Parkinson's disease
Zucca, F. A., Segura-Aguilar, J., Ferrari, E., Muñoz, P., Paris, I., Sulzer, D., Sarna, T., Casella, L., & Zecca, L. (2017) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2015.09.012 · Cited by 659
Self-citation
Protective and toxic roles of dopamine in Parkinson's disease
Segura‐Aguilar, J., Paris, I. B., Muñoz, P., Ferrari, E., Zecca, L., & Zucca, F. A. (2014) · Journal of Neurochemistry · doi:10.1111/jnc.12686 · Cited by 517
Biological metals and metal-targeting compounds in major neurodegenerative diseases
Barnham, K. J., & Bush, A. I. (2014) · Chem. Soc. Rev. · doi:10.1039/c4cs00138a · Cited by 497
Melanins and melanogenesis: from pigment cells to human health and technological applications
d’Ischia, M., Wakamatsu, K., Cicoira, F., Mauro, E. D., García-Borrón, J. C., Commo, S., Galván, I., Ghanem, G., Kenzo, K., Meredith, P., et al. (2015) · Pigment Cell & Melanoma Research · doi:10.1111/pcmr.12393 · Cited by 499
Current challenges in understanding melanogenesis: Bridging chemistry, biological control, morphology, and function
Simon, J. D., Peles, D., Wakamatsu, K., & Ito, S. (2009) · Pigment Cell & Melanoma Research · doi:10.1111/j.1755-148x.2009.00610.x · Cited by 391
MHC-I expression renders catecholaminergic neurons susceptible to T-cell-mediated degeneration
Cebrián, C., Zucca, F. A., Mauri, P., Steinbeck, J. A., Studer, L., Scherzer, C. R., Kanter, E., Budhu, S., Mandelbaum, J., Vonsattel, J. P., et al. (2014) · Nature Communications · doi:10.1038/ncomms4633 · Cited by 338
Iron in Neurodegeneration – Cause or Consequence?
Ndayisaba, A., Kaindlstorfer, C., & Wenning, G. K. (2019) · Frontiers in Neuroscience · doi:10.3389/fnins.2019.00180 · Cited by 305
What are melanocytesreallydoing all day long…?
Plonka, P. M., Passeron, T., Brenner, M., Tobin, D. J., Shibahara, S., Thomas, A. J., Slominski, A. T., Kadekaro, A. L., Hershkovitz, D., Peters, E. M. J., et al. (2009) · Experimental Dermatology · doi:10.1111/j.1600-0625.2009.00912.x · Cited by 318
From Extraction to Advanced Analytical Methods: The Challenges of Melanin Analysis
Pralea, I.-E., Moldovan, R.-C., Petrache, A.-M., Ilieș, M., Hegheş, S. C., Ielciu, I., Nicoară, R., Moldovan, M., Ene, M., Radu, M., et al. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms20163943 · Cited by 285
Determination of Melanin Synthetic Pathways
Hearing, V. J. (2011) · Journal of Investigative Dermatology · doi:10.1038/skinbio.2011.4 · Cited by 293
Neuromelanin detection by magnetic resonance imaging (MRI) and its promise as a biomarker for Parkinson’s disease
Sulzer, D., Cassidy, C., Horga, G., Kang, U. J., Fahn, S., Casella, L., Pezzoli, G., Langley, J. A., Hu, X. P., Zucca, F. A., et al. (2018) · npj Parkinson s Disease · doi:10.1038/s41531-018-0047-3 · Cited by 288
Dopamine, Oxidative Stress and Protein–Quinone Modifications in Parkinson's and Other Neurodegenerative Diseases
Monzani, E., Nicolis, S., Dell’Acqua, S., Capucciati, A., Bacchella, C., Zucca, F. A., Mosharov, E. V., Sulzer, D., Zecca, L., & Casella, L. (2018) · Angewandte Chemie International Edition · doi:10.1002/anie.201811122 · Cited by 274
Neuromelanin-sensitive MRI as a noninvasive proxy measure of dopamine function in the human brain
Cassidy, C., Zucca, F. A., Girgis, R. R., Baker, S. C., Weinstein, J. J., Sharp, M. E., Bellei, C., Valmadre, A., Vanegas‐Arroyave, N., Kegeles, L. S., et al. (2019) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1807983116 · Cited by 245
Neuromelanin of the Human Substantia Nigra: An Update
Zucca, F. A., Basso, E., Cupaioli, F. A., Ferrari, E., Sulzer, D., Casella, L., & Zecca, L. (2014) · Neurotoxicity Research · doi:10.1007/s12640-013-9435-y · Cited by 243
Neuromelanin marks the spot: identifying a locus coeruleus biomarker of cognitive reserve in healthy aging
Clewett, D., Lee, T., Greening, S. G., Ponzio, A., Margalit, E., & Mather, M. (2015) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2015.09.019 · Cited by 241
Quantification and Assessment of the Chemical Form of Residual Gadolinium in the Brain After Repeated Administration of Gadolinium-Based Contrast Agents
Frenzel, T., Apte, C. N., Jošt, G., Schöckel, L., Lohrke, J., & Pietsch, H. (2017) · Investigative Radiology · doi:10.1097/rli.0000000000000352 · Cited by 209
Iron, myelin, and the brain: neuroimaging meets neurobiology
Möller, H. E., Bossoni, L., Connor, J. R., Crichton, R. R., Does, M. D., Ward, R. J., Zecca, L., Zucca, F. A., & Ronen, I. (2019) · Trends in Neurosciences · doi:10.1016/j.tins.2019.03.009 · Cited by 207
Hypoxia, Oxidative Stress, and Inflammation: Three Faces of Neurodegenerative Diseases
Merelli, A., Repetto, M. G., Lazarowski, A., & Auzmendi, J. (2020) · Journal of Alzheimer s Disease · doi:10.3233/jad-201074 · Cited by 188
Melanin nanoparticles as a promising tool for biomedical applications – a review
Caldas, M., Paiva‐Santos, A. C., Veiga, F., Rebelo, R., Reis, R. L., & Correlo, V. M. (2020) · Acta Biomaterialia · doi:10.1016/j.actbio.2020.01.044 · Cited by 186
Melanin-based flexible supercapacitors
Kumar, P., Mauro, E. D., Zhang, S., Pezzella, A., Soavi, F., Santato, C., & Cicoira, F. (2016) · Journal of Materials Chemistry C · doi:10.1039/c6tc03739a · Cited by 165
The Aging of Iron Man
Ashraf, A., Clark, M., & So, P. (2018) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2018.00065 · Cited by 163
Cerebral Iron Deposition in Neurodegeneration
Dušek, P., Hofer, T., Alexander, J., Roos, P. M., & Aaseth, J. (2022) · Biomolecules · doi:10.3390/biom12050714 · Cited by 170
Chemical Reactivities of ortho-Quinones Produced in Living Organisms: Fate of Quinonoid Products Formed by Tyrosinase and Phenoloxidase Action on Phenols and Catechols
Ito, S., Sugumaran, M., & Wakamatsu, K. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21176080 · Cited by 157
Contrast mechanisms associated with neuromelanin‐MRI
Trujillo, P., Summers, P. E., Ferrari, E., Zucca, F. A., Sturini, M., Mainardi, L. T., Cerutti, S., Smith, A. K., Smith, S. A., Zecca, L., et al. (2016) · Magnetic Resonance in Medicine · doi:10.1002/mrm.26584 · Cited by 154
Neuromelanin organelles are specialized autolysosomes that accumulate undegraded proteins and lipids in aging human brain and are likely involved in Parkinson’s disease
Zucca, F. A., Vanna, R., Cupaioli, F. A., Bellei, C., Palma, A. D., Silvestre, D. D., Mauri, P., Grassi, S., Prinetti, A., Casella, L., et al. (2018) · npj Parkinson s Disease · doi:10.1038/s41531-018-0050-8 · Cited by 154
Parkinson's disease: Alterations in iron and redox biology as a key to unlock therapeutic strategies
Ma, L., Azad, M. G., Dharmasivam, M., Richardson, V., Quinn, R. J., Feng, Y., Pountney, D. L., Tonissen, K. F., Mellick, G. D., Yanatori, I., et al. (2021) · Redox Biology · doi:10.1016/j.redox.2021.101896 · Cited by 151
Disentangling eumelanin “black chromophore”: Visible absorption changes as signatures of oxidation state- and aggregation-dependent dynamic interactions in a model water-soluble 5,6-dihydroxyindole polymer
Pezzella, A., Iadonisi, A., Valerio, S., Panzella, L., Napolitano, A., Adinolfi, M., & d’Ischia, M. (2009) · Journal of the American Chemical Society · doi:10.1021/ja905162s · Cited by 147
Neuromelanin in Parkinson’s Disease: Tyrosine Hydroxylase and Tyrosinase
Nagatsu, T., Nakashima, A., Watanabe, H., Ito, S., & Wakamatsu, K. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23084176 · Cited by 144
Impact of Dopamine Oxidation on Dopaminergic Neurodegeneration
Zhang, S., Wang, R., & Wang, G. (2018) · ACS Chemical Neuroscience · doi:10.1021/acschemneuro.8b00454 · Cited by 133
Hepcidin Suppresses Brain Iron Accumulation by Downregulating Iron Transport Proteins in Iron-Overloaded Rats
Du, F., Qian, Z., Luo, Q., Yung, W., & Ke, Y. (2014) · Molecular Neurobiology · doi:10.1007/s12035-014-8847-x · Cited by 130
Effect of Off-Target Binding on 18F-Flortaucipir Variability in Healthy Controls Across the Life Span
Baker, S. L., Harrison, T. M., Maass, A., La Joie, R., & Jagust, W. J. (2019) · Journal of Nuclear Medicine · doi:10.2967/jnumed.118.224113 · Cited by 132
In vivo imaging of neuromelanin in Parkinson’s disease using18F-AV-1451 PET
Hansen, A. K., Knudsen, K., Lillethorup, T. P., Landau, A. M., Parbo, P., Fedorova, T., Audrain, H., Bender, D., Østergaard, K., Brooks, D. J., et al. (2016) · Brain · doi:10.1093/brain/aww098 · Cited by 128
Dopaminergic dysfunction and excitatory/inhibitory imbalance in treatment-resistant schizophrenia and novel neuromodulatory treatment
Wada, M., Noda, Y., Iwata, Y., Tsugawa, S., Yoshida, K., Tani, H., Hirano, Y., Koike, S., Sasabayashi, D., Katayama, H., et al. (2022) · Molecular Psychiatry · doi:10.1038/s41380-022-01572-0 · Cited by 113
Engineered nanoparticles, How brain friendly is this new guest?
Cupaioli, F. A., Zucca, F. A., Boraschi, D., & Zecca, L. (2014) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2014.05.002 · Cited by 139
Brain Imaging of Alzheimer Dementia Patients and Elderly Controls with 18F-MK-6240, a PET Tracer Targeting Neurofibrillary Tangles
Lohith, T. G., Bennacef, I., Vandenberghe, R., Vandenbulcke, M., Salinas, C. A., Declercq, R., Reynders, T., Telan-Choing, N. F., Riffel, K., Celen, S., et al. (2019) · Journal of Nuclear Medicine · doi:10.2967/jnumed.118.208215 · Cited by 107
Life span pigmentation changes of the substantia nigra detected by neuromelanin‐sensitive MRI
Xing, Y., Sapuan, A. H., Dineen, R. A., & Auer, D. P. (2018) · Movement Disorders · doi:10.1002/mds.27502 · Cited by 105
MRI biomarkers of motor and non-motor symptoms in Parkinson's disease
Ryman, S. G., & Poston, K. L. (2019) · Parkinsonism & Related Disorders · doi:10.1016/j.parkreldis.2019.10.002 · Cited by 106
Quadruple abnormal protein aggregates in brainstem pathology and exogenous metal-rich magnetic nanoparticles (and engineered Ti-rich nanorods). The substantia nigrae is a very early target in young urbanites and the gastrointestinal tract a key brainstem portal
Calderón‐Garcidueñas, L., González-Maciel, A., Reynoso-Robles, R., Hammond, J., Kulesza, R. J., Lachmann, I., Torres‐Jardón, R., Mukherjee, P. S., & Maher, B. A. (2020) · Environmental Research · doi:10.1016/j.envres.2020.110139 · Cited by 98
Interactions of dopamine, iron, and alpha-synuclein linked to dopaminergic neuron vulnerability in Parkinson's disease and Neurodegeneration with Brain Iron Accumulation disorders
Wise, R. M., Wagener, A., Fietzek, U. M., Klopstock, T., Mosharov, E. V., Zucca, F. A., Sulzer, D., Zecca, L., & Burbulla, L. F. (2022) · Neurobiology of Disease · doi:10.1016/j.nbd.2022.105920 · Cited by 96
Off-Target 18F-AV-1451 Binding in the Basal Ganglia Correlates with Age-Related Iron Accumulation
Choi, J. Y., Cho, H., Ahn, S. J., Lee, J., Ryu, Y. H., Lee, M. S., & Lyoo, C. H. (2017) · Journal of Nuclear Medicine · doi:10.2967/jnumed.117.195248 · Cited by 96
Iron accumulation in Bruch's membrane and melanosomes of donor eyes with age-related macular degeneration
Biesemeier, A., Yoeruek, E., Eibl, O., & Schraermeyer, U. (2015) · Experimental Eye Research · doi:10.1016/j.exer.2015.05.019 · Cited by 86
Aminochrome Induces Disruption of Actin, Alpha-, and Beta-Tubulin Cytoskeleton Networks in Substantia-Nigra-Derived Cell Line
Paris, I. B., Perez-Pastene, C., Cárdenas, S., Iturra, P., Muñoz, P., Couve, E., Caviedes, P. A., & Segura‐Aguilar, J. (2010) · Neurotoxicity Research · doi:10.1007/s12640-009-9148-4 · Cited by 89
Preserving Lysosomal Function in the Aging Brain: Insights from Neurodegeneration
Peng, W., Minakaki, G., Nguyen, M., & Krainc, D. (2019) · Neurotherapeutics · doi:10.1007/s13311-019-00742-3 · Cited by 79
Reproducibility assessment of neuromelanin-sensitive magnetic resonance imaging protocols for region-of-interest and voxelwise analyses
Wengler, K., He, X., Abi‐Dargham, A., & Horga, G. (2019) · NeuroImage · doi:10.1016/j.neuroimage.2019.116457 · Cited by 82
Neuromelanins of Human Brain Have Soluble and Insoluble Components with Dolichols Attached to the Melanic Structure
Engelen, M., Vanna, R., Bellei, C., Zucca, F. A., Wakamatsu, K., Monzani, E., Ito, S., Casella, L., & Zecca, L. (2012) · PLoS ONE · doi:10.1371/journal.pone.0048490 · Cited by 77
DNAJC12 and dopa‐responsive nonprogressive parkinsonism
Straniero, L., Guella, I., Cilia, R., Parkkinen, L., Rimoldi, V., Young, A., Asselta, R., Soldà, G., Sossi, V., Stoessl, A. J., et al. (2017) · Annals of Neurology · doi:10.1002/ana.25048 · Cited by 77
Norepinephrine and its metabolites are involved in the synthesis of neuromelanin derived from the locus coeruleus
Wakamatsu, K., Tabuchi, K., Ojika, M., Zucca, F. A., Zecca, L., & Ito, S. (2015) · Journal of Neurochemistry · doi:10.1111/jnc.13237 · Cited by 76
Autophagy protects against aminochrome-induced cell death in substantia nigra-derived cell line.
Paris, I., Muñoz, P., Huenchuguala, S., Couve, E., Sanders, L. H., Greenamyre, J., Caviedes, P., & Segura-Aguilar, J. (2011) · Toxicological Sciences · doi:10.1093/toxsci/kfr060 · Cited by 69
Neuromelanins in brain aging and Parkinson's disease: synthesis, structure, neuroinflammatory, and neurodegenerative role
Zucca, F. A., Capucciati, A., Bellei, C., Sarna, M., Sarna, T., Monzani, E., Casella, L., & Zecca, L. (2023) · IUBMB Life · doi:10.1002/iub.2654 · Cited by 69
Unraveling the contributions to the neuromelanin-MRI contrast
Priovoulos, N., van Boxel, S. C. J., Jacobs, H. I. L., Poser, B. A., Uludaǧ, K., Verhey, F. R. J., & Ivanov, D. (2020) · Brain Structure and Function · doi:10.1007/s00429-020-02153-z · Cited by 77
Neuromelanin-sensitive MRI as a promising biomarker of catecholamine function
Trujillo, P., Aumann, M. A., & Claassen, D. O. (2023) · Brain · doi:10.1093/brain/awad300 · Cited by 79
Melanin and neuromelanin binding of drugs and chemicals: toxicological implications
Karlsson, O., & Lindquist, N. G. (2016) · Archives of Toxicology · doi:10.1007/s00204-016-1757-0 · Cited by 73
Melanin pigment derived from marine organisms and its industrial applications
Ghattavi, K., Homaei, A. A., Kamrani, E., & Kim, S. (2022) · Dyes and Pigments · doi:10.1016/j.dyepig.2022.110214 · Cited by 70
Cellular and Molecular Aspects of the β-N-Methylamino-l-alanine (BMAA) Mode of Action within the Neurodegenerative Pathway: Facts and Controversy
Delcourt, N., Claudepierre, T., Maignien, T., Arnich, N., & Mattei, C. (2017) · Toxins · doi:10.3390/toxins10010006 · Cited by 68
Uptake of environmental toxicants by the locus ceruleus: A potential trigger for neurodegenerative, demyelinating and psychiatric disorders
Pamphlett, R. (2013) · Medical Hypotheses · doi:10.1016/j.mehy.2013.11.016 · Cited by 70
Elemental mapping of Neuromelanin organelles of human Substantia Nigra: correlative ultrastructural and chemical analysis by analytical transmission electron microscopy and nano‐secondary ion mass spectrometry
Biesemeier, A., Eibl, O., Eswara, S., Audinot, J., Wirtz, T., Pezzoli, G., Zucca, F. A., Zecca, L., & Schraermeyer, U. (2016) · Journal of Neurochemistry · doi:10.1111/jnc.13648 · Cited by 68
Isometric exercise facilitates attention to salient events in women via the noradrenergic system
Mather, M., Huang, R., Clewett, D., Nielsen, S. E., Velasco, R., Tu, K., Han, S., & Kennedy, B. L. (2020) · NeuroImage · doi:10.1016/j.neuroimage.2020.116560 · Cited by 67
The Neuromelanin Paradox and Its Dual Role in Oxidative Stress and Neurodegeneration
Moreno-García, A., Kun, A., Calero, M., & Calero, O. (2021) · Antioxidants · doi:10.3390/antiox10010124 · Cited by 66
Quantifying changes in nigrosomes using quantitative susceptibility mapping and neuromelanin imaging for the diagnosis of early-stage Parkinson’s disease
Takahashi, H., Watanabe, Y., Tanaka, H., Mihara, M., Mochizuki, H., Liu, T., Wang, Y., & Tomiyama, N. (2018) · British Journal of Radiology · doi:10.1259/bjr.20180037 · Cited by 65
Functional Mammalian Amyloids and Amyloid-Like Proteins
Rubel, M. S., Fedotov, S. A., Grizel, A. V., Sopova, J. V., Malikova, O. A., Chernoff, Y. O., & Rubel, A. A. (2020) · Life · doi:10.3390/life10090156 · Cited by 61
Recent Advances in Characterization of Melanin Pigments in Biological Samples
Wakamatsu, K., & Ito, S. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms24098305 · Cited by 64
Biosynthetic pathway to neuromelanin and its aging process
Wakamatsu, K., Murase, T., Zucca, F. A., Zecca, L., & Ito, S. (2012) · Pigment Cell & Melanoma Research · doi:10.1111/pcmr.12014 · Cited by 58
The role of tyrosine hydroxylase as a key player in neuromelanin synthesis and the association of neuromelanin with Parkinson’s disease
Nagatsu, T., Nakashima, A., Watanabe, H., Ito, S., Wakamatsu, K., Zucca, F. A., Zecca, L., Youdim, M. B. H., Wulf, M., Riederer, P. F., et al. (2023) · Journal of Neural Transmission · doi:10.1007/s00702-023-02617-6 · Cited by 57
Dysregulation of tyrosinase activity: a potential link between skin disorders and neurodegeneration
Jin, W., Stehbens, S. J., Barnard, R. T., Blaskovich, M. A. T., & Ziora, Z. M. (2023) · Journal of Pharmacy and Pharmacology · doi:10.1093/jpp/rgad107 · Cited by 55
Classical and Nonclassical Melanocytes in Vertebrates
Colombo, S., Berlin, I., Delmas, V., & Larue, L. (2011) · Wiley eBooks · doi:10.1002/9783527636150.ch2 · Cited by 52
Pragmatic Approach on Neuroimaging Techniques for the Differential Diagnosis of Parkinsonisms
Peralta, C., Strafella, A. P., van Eimeren, T., Ceravolo, R., Seppi, K., Kaasinen, V., Arena, J., Lehéricy, S., & the International Parkinson Movement Disorders Society‐Neuroimaging Study Group (2021) · Movement Disorders Clinical Practice · doi:10.1002/mdc3.13354 · Cited by 53
Comprehensive MRI quantification of the substantia nigra pars compacta in Parkinson’s disease
Takahashi, H., Watanabe, Y., Tanaka, H., Mihara, M., Mochizuki, H., Takahashi, K., Yamamoto, K., Liu, T., Wang, Y., & Tomiyama, N. (2018) · European Journal of Radiology · doi:10.1016/j.ejrad.2018.06.024 · Cited by 53
MAO-B Inhibitors Do Not Block In Vivo Flortaucipir([18F]-AV-1451) Binding
Hansen, A. K., Brooks, D. J., & Borghammer, P. (2018) · Molecular Imaging and Biology · doi:10.1007/s11307-017-1143-1 · Cited by 51
Biomimetic fabrication of information-rich phenolic-chitosan films
Gray, K. M., Kim, E., Wu, L., Liu, Y., Bentley, W. E., & Payne, G. F. (2011) · Soft Matter · doi:10.1039/c1sm05293d · Cited by 53
Zinc‐induced Structural Effects Enhance Oxygen Consumption and Superoxide Generation in Synthetic Pheomelanins on UVA/Visible Light Irradiation†
Panzella, L., Szewczyk, G., D’Ischia, M., Napolitano, A., & Sarna, T. (2010) · Photochemistry and Photobiology · doi:10.1111/j.1751-1097.2010.00726.x · Cited by 50
NRF2 Activation and Downstream Effects: Focus on Parkinson’s Disease and Brain Angiotensin
Parga, J. A., Rodriguez-Perez, A. I., García-Garrote, M., Rodríguez‐Pallares, J., & Labandeira-García, J. L. (2021) · Antioxidants · doi:10.3390/antiox10111649 · Cited by 56
Chemical composition of melanosomes, lipofuscin and melanolipofuscin granules of human RPE tissues
Biesemeier, A., Schraermeyer, U., & Eibl, O. (2011) · Experimental Eye Research · doi:10.1016/j.exer.2011.04.004 · Cited by 52
Binding and Reactivity of Copper to R1 and R3 Fragments of tau Protein
Bacchella, C., Gentili, S., Bellotti, D., Quartieri, E., Draghi, S., Baratto, M. C., Remelli, M., Valensin, D., Monzani, E., Nicolis, S., et al. (2019) · Inorganic Chemistry · doi:10.1021/acs.inorgchem.9b02266 · Cited by 51
Toxic Feedback Loop Involving Iron, Reactive Oxygen Species, α-Synuclein and Neuromelanin in Parkinson’s Disease and Intervention with Turmeric
van Rensburg, Z. J., Abrahams, S., Bardien, S., & Kenyon, C. P. (2021) · Molecular Neurobiology · doi:10.1007/s12035-021-02516-5 · Cited by 52
Naturally Derived Melanin Nanoparticle Composites with High Electrical Conductivity and Biodegradability
Eom, T., Jeon, J., Lee, S., Woo, K., Heo, J. E., Martin, D. C., Wie, J. J., & Shim, B. S. (2019) · Particle & Particle Systems Characterization · doi:10.1002/ppsc.201900166 · Cited by 49
Evidence for Dopamine Abnormalities in the Substantia Nigra in Cocaine Addiction Revealed by Neuromelanin-Sensitive MRI
Cassidy, C., Carpenter, K. M., Konova, A. B., Cheung, V., Grassetti, A., Zecca, L., Abi‐Dargham, A., Martinez, D., & Horga, G. (2020) · American Journal of Psychiatry · doi:10.1176/appi.ajp.2020.20010090 · Cited by 47
Parkinson’s Disease: Cells Succumbing to Lifelong Dopamine-Related Oxidative Stress and Other Bioenergetic Challenges
Watanabe, H., Dijkstra, J. M., & Nagatsu, T. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms25042009 · Cited by 48
Synthesis, Structure Characterization, and Evaluation in Microglia Cultures of Neuromelanin Analogues Suitable for Modeling Parkinson’s Disease
Ferrari, E., Capucciati, A., Prada, I., Zucca, F. A., D’Arrigo, G., Pontiroli, D., Bridelli, M. G., Sturini, M., Bubacco, L., Monzani, E., et al. (2016) · ACS Chemical Neuroscience · doi:10.1021/acschemneuro.6b00231 · Cited by 46
Iron transport in Parkinson's disease
Hirsch, É. C. (2009) · Parkinsonism & Related Disorders · doi:10.1016/s1353-8020(09)70816-8 · Cited by 46
Neuromelanin in parkinsonian disorders: an update
Martín‐Bastida, A., Pietracupa, S., & Piccini, P. P. (2017) · International Journal of Neuroscience · doi:10.1080/00207454.2017.1325883 · Cited by 44
Solid-state NMR spectroscopy identifies three classes of lipids in Cryptococcus neoformans melanized cell walls and whole fungal cells
Chrissian, C., Camacho, E., Kelly, J. E., Wang, H., Casadevall, A., & Stark, R. E. (2020) · Journal of Biological Chemistry · doi:10.1074/jbc.ra120.015201 · Cited by 41
Insects synthesize pheomelanin
Galván, I., Jorge, A., Edelaar, P., & Wakamatsu, K. (2015) · Pigment Cell & Melanoma Research · doi:10.1111/pcmr.12397 · Cited by 40
Aminochrome Toxicity is Mediated by Inhibition of Microtubules Polymerization Through the Formation of Adducts with Tubulin
Briceño, A., Muñoz, P., Brito, P., Huenchuguala, S., Segura‐Aguilar, J., & Paris, I. B. (2015) · Neurotoxicity Research · doi:10.1007/s12640-015-9560-x · Cited by 40
Fungal Melanins Differ in Planar Stacking Distances
Casadevall, A., Nakouzi, A. S., Crippa, P. R., & Eisner, M. (2012) · PLoS ONE · doi:10.1371/journal.pone.0030299 · Cited by 39
Chemiexcitation and Its Implications for Disease
Brash, D. E., Gonçalves, L. C. P., & Bechara, E. J. H. (2018) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2018.04.004 · Cited by 37
Neuromelanin accumulation in patients with schizophrenia: A systematic review and meta-analysis
Ueno, F., Iwata, Y., Nakajima, S., Caravaggio, F., Rubio, J. M., Horga, G., Cassidy, C., Torres‐Carmona, E., Luca, V. D., Tsugawa, S., et al. (2021) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2021.10.028 · Cited by 35
Biogenic Amines in Rett Syndrome: The Usual Suspects
Roux, J., & Villard, L. (2009) · Behavior Genetics · doi:10.1007/s10519-009-9303-y · Cited by 37
The toxic metal hypothesis for neurological disorders
Pamphlett, R., & Bishop, D. (2023) · Frontiers in Neurology · doi:10.3389/fneur.2023.1173779 · Cited by 44
Interaction of Neuromelanin with Xenobiotics and Consequences for Neurodegeneration; Promising Experimental Models
Capucciati, A., Zucca, F. A., Monzani, E., Zecca, L., Casella, L., & Hofer, T. (2021) · Antioxidants · doi:10.3390/antiox10060824 · Cited by 36
Heavy metals in locus ceruleus and motor neurons in motor neuron disease
Pamphlett, R., & Jew, S. K. (2013) · Acta Neuropathologica Communications · doi:10.1186/2051-5960-1-81 · Cited by 36
Neuromelanin Modulates Heterocyclic Aromatic Amine-Induced Dopaminergic Neurotoxicity
Lawana, V., Um, S. Y., Rochet, J., Turesky, R. J., Shannahan, J. H., & Cannon, J. R. (2019) · Toxicological Sciences · doi:10.1093/toxsci/kfz210 · Cited by 36
The Pigment in Alkaptonuria Relationship to Melanin and Other Coloured Substances: A Review of Metabolism, Composition and Chemical Analysis
Roberts, N. B., Curtis, S. A., Milan, A. M., & Ranganath, L. R. (2015) · JIMD Reports · doi:10.1007/8904_2015_453 · Cited by 34
Using Sepia melanin as a PD model to describe the binding characteristics of neuromelanin – A critical review
Schroeder, R. L., Double, K. L., & Gerber, C. (2015) · Journal of Chemical Neuroanatomy · doi:10.1016/j.jchemneu.2015.02.001 · Cited by 34
Synthesis and structural characterization of soluble neuromelanin analogs provides important clues to its biosynthesis
Ferrari, E., Engelen, M., Monzani, E., Sturini, M., Girotto, S., Bubacco, L., Zecca, L., & Casella, L. (2012) · JBIC Journal of Biological Inorganic Chemistry · doi:10.1007/s00775-012-0951-7 · Cited by 34
Riddles in the dark: Decoding the relationship between neuromelanin and neurodegeneration in locus coeruleus neurons
Iannitelli, A. F., & Weinshenker, D. (2023) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2023.105287 · Cited by 35
Heterogeneity of neural crest-derived melanocytes
Cichorek, M., Wachulska, M., & Skoniecka, A. (2013) · Open Life Sciences · doi:10.2478/s11535-013-0141-1 · Cited by 36
Matching ex vivo MRI With Iron Histology: Pearls and Pitfalls
De Barros, A., Arribarat, G., Combis, J., Chaynes, P., & Péran, P. (2019) · Frontiers in Neuroanatomy · doi:10.3389/fnana.2019.00068 · Cited by 31
A functionalized hydroxydopamine quinone links thiol modification to neuronal cell death
Farzam, A., Chohan, K. L., Strmiskova, M., Hewitt, S. J., Park, D. S., Pezacki, J. P., & Özcelik, D. (2019) · Redox Biology · doi:10.1016/j.redox.2019.101377 · Cited by 31

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

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review

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

Abstract

Overview

Integrity signals

Verification

Claims the paper makes

Claims other papers make about this one

Citations

Cites

Cited by

Related

Metadata

Record

About these checks