Affiliations: [a] Neurobiology Group, Division of Biochemical Sciences, CSIR-National Chemical Laboratory, Pune, India
| [b] Academy of Scientific and Innovative Research (AcSIR), New Delhi, India
Correspondence:
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Correspondence to: Dr. Subashchandrabose Chinnathambi, Neurobiology group, Division of Biochemical Sciences, CSIR-National Chemical Laboratory (CSIR-NCL), Dr. Homi Bhabha Road, 411008 Pune, India. Tel.: +91 20 25902232; Fax: +91 20 25902648; E-mail: s.chinnathambi@ncl.res.in.
Abstract: Alzheimer’s disease (AD) is one of the major age related neurodegenerative diseases whose pathology arises due to the presence of two distinct protein aggregates, viz., amyloid-β plaques in extracellular matrix and tau neurofibrillary tangles in neurons. Multiple factors play a role in AD pathology, which includes familial mutations, oxidative stress, and post-translational modifications. Melatonin is an endocrine hormone, secreted during darkness, derived from tryptophan, and produced mainly by the pineal gland. It is an amphipathic molecule, which makes it suitable to cross not only blood-brain barrier, but also to enter several other subcellular compartments like mitochondria and endoplasmic reticulum. In this context, the neuroprotective effect of melatonin may be attributed to its role as an antioxidant. Melatonin’s pleiotropic function as an antioxidant and neuroprotective agent has been widely studied. However, its direct effect on the aggregation of tau and amyloid-β needs to be explored. Furthermore, an important aspect of its function is its ability to regulate the process of phosphorylation of tau by affecting the function of kinases and phosphatases. In this review, we are focusing on the pleiotropic function of melatonin on the aspect of its neuroprotective function in tau pathology, which includes antioxidant function, regulation of enzymes, including kinases and enzymes involved in free radical scavenging and mitochondrial protection.
Keywords: Alzheimer’s disease, hyperphosphorylation, melatonin, mitochondria, protein aggregation, tau protein
