{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T17:41:40Z","timestamp":1790358100869,"version":"4.1.0"},"reference-count":127,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2025,12,30]],"date-time":"2025-12-30T00:00:00Z","timestamp":1767052800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"DoW\/USU Brain Tissue Repository and the Neuropathology Research Program","award":["USU # PAT-74-10982"],"award-info":[{"award-number":["USU # PAT-74-10982"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Melanin pigments are ubiquitous biopolymers across diverse life forms and play multifaceted roles in cellular defense and environmental adaptation. The specialized neuromelanin in human brains accumulates mainly within catecholaminergic neurons of the substantia nigra and locus coeruleus, serving as a crucial modulator of brain homeostasis, metal detoxification, and oxidative stress responses. The intricate processes of human melanogenesis, encompassing both cutaneous and neuronal forms, are governed by complex genetic networks. Concurrently, melanin in fungi (synthesized through distinct genetic pathways) confers remarkable resistance to environmental stressors, including ionizing radiation. Recent advancements in omics technologies\u2014including transcriptomics, proteomics, metabolomics, and epigenomics\u2014have profoundly enhanced our understanding of neuromelanin\u2019s molecular environment in health, aging, and neurodegenerative conditions such as Parkinson\u2019s disease (PD), Alzheimer\u2019s disease (AD), and other neurological disorders. This article reviews the genetic underpinnings of human melanogenesis and fungal melanogenesis, explores the convergent and divergent evolutionary pressures driving their functions, and synthesizes the rapidly accumulating omics data to elucidate neuromelanin\u2019s critical, and often dual, role in human brain pathology. Moreover, we discuss the intriguing parallels between neuromelanin and fungal melanin, highlighting radioprotection and its potential implications for neuroprotection and astrobiology, with a special emphasis on the need to investigate neuromelanin\u2019s potential for radioprotection in light of fungal melanin\u2019s remarkable protective properties.<\/jats:p>","DOI":"10.3390\/biom16010061","type":"journal-article","created":{"date-parts":[[2025,12,31]],"date-time":"2025-12-31T16:34:23Z","timestamp":1767198863000},"page":"61","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Melanin and Neuromelanin in Humans: Insights Across Health, Aging, Diseases, and Unexpected Aspects of Fungal Melanogenesis"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4804-8877","authenticated-orcid":false,"given":"Kathleen","family":"Hatch","sequence":"first","affiliation":[{"name":"DoW\/USU Brain Tissue Repository & Neuropathology Program, Uniformed Services University (USU), Bethesda, MD 20814, USA"},{"name":"Department of Pathology, F. Edward H\u00e9bert School of Medicine, Uniformed Services University (USU), Bethesda, MD 20814, USA"},{"name":"The Henry M. Jackson Foundation for the Advancement of Military Medicine (HJF) Inc., Bethesda, MD 20817, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3510-5323","authenticated-orcid":false,"given":"Erin K.","family":"Murphy","sequence":"additional","affiliation":[{"name":"DoW\/USU Brain Tissue Repository & Neuropathology Program, Uniformed Services University (USU), Bethesda, MD 20814, USA"},{"name":"Department of Pathology, F. Edward H\u00e9bert School of Medicine, Uniformed Services University (USU), Bethesda, MD 20814, USA"},{"name":"The Henry M. Jackson Foundation for the Advancement of Military Medicine (HJF) Inc., Bethesda, MD 20817, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Radam\u00e9s J. B.","family":"Cordero","sequence":"additional","affiliation":[{"name":"Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21205, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5511-0950","authenticated-orcid":false,"given":"Diego","family":"Iacono","sequence":"additional","affiliation":[{"name":"DoW\/USU Brain Tissue Repository & Neuropathology Program, Uniformed Services University (USU), Bethesda, MD 20814, USA"},{"name":"Department of Pathology, F. Edward H\u00e9bert School of Medicine, Uniformed Services University (USU), Bethesda, MD 20814, USA"},{"name":"The Henry M. Jackson Foundation for the Advancement of Military Medicine (HJF) Inc., Bethesda, MD 20817, USA"},{"name":"Department of Neurology, F. Edward H\u00e9bert School of Medicine, Uniformed Services University (USU), Bethesda, MD 20814, USA"},{"name":"Neuroscience Program, Department of Anatomy, Physiology & Genetics, Uniformed Services University (USU), Bethesda, MD 20814, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,12,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1235","DOI":"10.1016\/S1357-2725(97)00013-7","article-title":"Melanin","volume":"29","author":"Riley","year":"1997","journal-title":"Int. J. Biochem. Cell Biol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1185","DOI":"10.1152\/physrev.00044.2003","article-title":"Melanin Pigmentation in Mammalian Skin and Its Hormonal Regulation","volume":"84","author":"Slominski","year":"2004","journal-title":"Physiol. 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