Melatonin regulates Aβ production/clearance balance and Aβ neurotoxicity: A potential therapeutic molecule for Alzheimer's disease

Alzheimer's disease (AD) is an age-related neurodegenerative disease with multiple predisposing factors and complicated pathogenesis. A beta peptide is one of the most important pathogenic factors in the etiology of AD. Accumulating evidence indicates that the imbalance of A beta production and A beta clearance in the brain of AD pa-tients leads to A beta deposition and neurotoxic A beta oligomer formation. Melatonin shows a potent neuroprotective effect and can prevent or slow down the progression of AD, supporting the view that melatonin is a potential therapeutic molecule for AD. Melatonin modulates the regulatory network of secretase expression and affects the function of secretase, thereby inhibiting amyloidogenic APP processing and A beta production. Additionally, melatonin ameliorates A beta-induced neurotoxicity and probably promotes A beta clearance through glymphaticlymphatic drainage, BBB transportation and degradation pathways. In this review, we summarize and discuss the role of melatonin against A beta-dependent AD pathogenesis. We explore the potential cellular and molecular mechanisms of melatonin on A beta production and assembly, A beta clearance, A beta neurotoxicity and circadian cycle disruption. We summarize multiple clinical trials of melatonin treatment in AD patients, showing that melatonin has a promising effect on improving sleep quality and cognitive function. This review aims to stimulate further research on melatonin as a potential therapeutic agent for AD.