Crosstalk between copper, Alzheimer’s disease, and melatonin

Abstract

Alzheimer’s disease (AD) is a neurodegenerative disorder that causes cognitive impairment and loss of neurons. According to the Alzheimer’s Association’s 2022 US report, the USA saw a 145% increase in AD-related fatalities from 2000 to 2020, with an estimated financial burden of these disorders surpassing $1 trillion annually. Its pathological features include neurofibrillary tangles and amyloid-beta (Aβ) plaques. Although there is presently no treatment that may stop the growth of AD, new clinical trials have suggested that anti-amyloid disease-modifying drugs may reduce the progression of the illness. According to a recent study, Copper (Cu) dysregulation plays a crucial role in AD pathogenesis by causing oxidative stress and encouraging the aggregation of Aβ. Meanwhile, melatonin, a neurohormone with strong neuroprotective, antioxidant, and Cu chelation qualities, has drawn an interest due to its possible use for AD treatment. This review thoroughly summarizes the most recent research, including in vivo, in vitro, and human studies, and also examines the complex relationships among AD, melatonin, and Cu toxicity. We observe how an excess of Cu aggravates AD pathogenesis and how the special qualities of melatonin can counteract these effects. Melatonin is a promising molecule having a dual approach to address pathogenesis of AD by chelating excess Cu and lowering oxidative stress. Comprehending the interplay between Cu dysregulation and the protective mechanisms of melatonin may result in innovative therapies, providing promises for enhanced management of AD.