Melanin and Neuromelanin in Humans: Insights Across Health, Aging, Diseases, and Unexpected Aspects of Fungal Melanogenesis

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-including transcriptomics, proteomics, metabolomics, and epigenomics-have profoundly enhanced our understanding of neuromelanin's molecular environment in health, aging, and neurodegenerative conditions such as Parkinson's disease (PD), Alzheimer's 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's 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's potential for radioprotection in light of fungal melanin's remarkable protective properties.