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

Sonali Sundram; Rishabha Malviya; Rajendra Awasthi

doi:10.2174/1871527321666220901125730

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

CNS Neurol Disord Drug Targets. 2022 Sep 1. doi: 10.2174/1871527321666220901125730. Online ahead of print.

Authors

Sonali Sundram^{1

2}, Rishabha Malviya¹, Rajendra Awasthi³

Affiliations

¹ Department of Pharmacy, School of Medical and Allied Sciences, Galgotias University, Greater Noida, U.P., India.
² Amity Institute of Pharmacy, Amity University Uttar Pradesh, Sector-125, Noida 201313, India.
³ Department of Pharmaceutical Sciences, School of Health Science and Technology, University of Petroleum and Energy Studies (UPES), Energy Acres, Bidholi, Via-Prem Nagar, Dehradun - 248 007, Uttarakhand, India.

PMID: 36056839
DOI: 10.2174/1871527321666220901125730

Abstract

Dementia is a global health concern owing to its complexity, which also poses a great challenge to pharmaceutical scientists and neuroscientists. The global dementia prevalence 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 non-amyloidogenic 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; biochemical.; genetic manipulation; hormonal disbalance; melatonin; neurological disorders.