Title:Genetic Causes of Alzheimer’s Disease and the Neuroprotective Role of
Melatonin in its Management
Volume: 22
Issue: 9
Author(s): Sonali Sundram, Rishabha Malviya and Rajendra Awasthi*
Affiliation:
- Department of
Pharmaceutical Sciences, School of Health Sciences and Technology, University of Petroleum and Energy Studies
(UPES), Energy Acres, Bidholi, Via-Prem Nagar, Dehradun - 248 007, Uttarakhand, India
Keywords:
Alzheimer’s disease, neurological disorders, melatonin, genetic manipulation, hormonal disbalance, biochemical.
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.