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Genetic Causes of Alzheimer’s Disease and the Neuroprotective Role of Melatonin in its Management

Author(s): Sonali Sundram, Rishabha Malviya and Rajendra Awasthi*

Volume 22, Issue 9, 2023

Published on: 23 September, 2022

Page: [1302 - 1312] Pages: 11

DOI: 10.2174/1871527321666220901125730

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Abstract

Dementia is a global health concern owing to its complexity, which also poses a great challenge to pharmaceutical scientists and neuroscientists. The global prevalence of dementia is approximately 47 million, which may increase by three times by 2050. Alzheimer’s disease (AD) is the most common cause of dementia. AD is a severe age-related neurodegenerative disorder characterized by short-term memory loss, aphasia, mood imbalance, and executive function. The etiology of AD is still unknown, and the exact origin of the disease is still under investigation. Aggregation of amyloid β (Aβ) plaques or neurotoxic Aβo oligomers outside the neuron is the most common cause of AD development. Amyloid precursor protein (APP) processing by β secretase and γ secretase produces abnormal Aβ monomers. This aggregation of Aβ and NFT is promoted by various genes like BACE1, ADAM10, PIN1, GSK-3, APOE, PPARα, etc. Identification of these genes can discover several therapeutic targets that can be useful in studying pathogenesis and underlying treatments. Melatonin modulates the activities of these genes, thereby reducing Aβ production and increasing its clearance. Melatonin also reduces the expression of APP by attenuating cAMP, thereby enhancing the nonamyloidogenic process. Present communication explored and discussed the neuroprotective role of melatonin against Aβ-dependent AD pathogenesis. The manuscript also discussed potential molecular and genetic mechanisms of melatonin in the production and clearance of Aβ that could ameliorate neurotoxicity.

Keywords: Alzheimer’s disease, neurological disorders, melatonin, genetic manipulation, hormonal disbalance, biochemical.

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