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Therapeutic potential of melatonin and its derivatives in aging and neurodegenerative diseases


Aging is associated with increasing impairments in brain homeostasis and represents the main risk factor across most neurodegenerative disorders. Melatonin, a neuroendocrine hormone that regulates mammalian chronobiology and endocrine functions is well known for its antioxidant potential, exhibiting both cytoprotective and chronobiotic abilities. Age-related decline of melatonin disrupting mitochondrial homeostasis and cytosolic DNA-mediated inflammatory reactions in neurons is a major contributory factor in the emergence of neurological abnormalities. There is scattered literature on the possible use of melatonin against neurodegenerative mechanisms in the aging process and its associated diseases. We have searched PUBMED with many combinations of key words for available literature spanning two decades. Based on the vast number of experimental papers, we hereby review recent advancements concerning the potential impact of melatonin on cellular redox balance and mitochondrial dynamics in the context of neurodegeneration. Next, we discuss a broader explanation of the involvement of disrupted redox homeostasis in the pathophysiology of age-related diseases and its connection to circadian mechanisms. Our effort may result in the discovery of novel therapeutic approaches. Finally, we summarize the current knowledge on molecular and circadian regulatory mechanisms of melatonin to overcome neurodegenerative diseases (NDDs) such as Alzheimer’s, Parkinson’s, Huntington’s disease, and amyotrophic lateral sclerosis, however, these findings need to be confirmed by larger, well-designed clinical trials. This review is also expected to uncover the associated molecular alterations in the aging brain and explain how melatonin-mediated circadian restoration of neuronal homeodynamics may increase healthy lifespan in age-related NDDs.

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AKV gratefully acknowledges the Council of Scientific and Industrial Research (CSIR), Government of India for providing financial support in the form of a Senior Research Fellowship (09/001(0426)/2018-EMR-I). The Department of Biotechnology, Government of India, provided financial support for this work through a project of “Research Resources, Service Facilities, and Platforms”. The FIST Grant of DST, New Delhi, and SAP DRS I from the UGC, India, both provide funding for the Department of Biochemistry.

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AKV prepared the first draft of the manuscript. The figures were prepared by AKV and SS. SIR assisted with subsequent drafts of the manuscript. All authors have read and approved the final version of the manuscript.

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Correspondence to Syed Ibrahim Rizvi.

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Verma, A.K., Singh, S. & Rizvi, S.I. Therapeutic potential of melatonin and its derivatives in aging and neurodegenerative diseases. Biogerontology 24, 183–206 (2023).

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