Abstract
Alzheimer’s disease (AD), an age-related neurodegenerative disorder with progressive cognition deficit, is characterized by extracellular senile plaques (SP) of aggregated β-amyloid (Aβ) and intracellular neurofibrillary tangles, mainly containing the hyperphosphorylated microtubule-associated protein tau. Multiple factors contribute to the etiology of AD in terms of initiation and progression. Melatonin is an endogenously produced hormone in the brain and decreases during aging and in patients with AD. Data from clinical trials indicate that melatonin supplementation improves sleep, ameliorates sundowning and slows down the progression of cognitive impairment in AD patients. Melatonin efficiently protects neuronal cells from Aβ-mediated toxicity via antioxidant and anti-amyloid properties. It not only inhibits Aβ generation, but also arrests the formation of amyloid fibrils by a structure-dependent interaction with Aβ. Our studies have demonstrated that melatonin efficiently attenuates Alzheimer-like tau hyperphosphorylation. Although the exact mechanism is still not fully understood, a direct regulatory influence of melatonin on the activities of protein kinases and protein phosphatases is proposed. Additionally, melatonin also plays a role in protecting the cholinergic system and in anti-inflammation. The aim of this review is to stimulate interest in melatonin as a potentially useful agent in the prevention and treatment of AD.
Highlights
Alzheimer’s disease (AD) is an age-associated neurodegenerative disease and characterized by progressive loss of cognition and other neurobehavioral manifestations
Its indirect antioxidant effects and anti-amyloid effects are based on the support of appropriate circadian phasing and anti-excitotoxic actions [68,143]
It is not surprising that melatonin is protective in numerous experimental systems and has been proposed as a treatment for AD
Summary
Alzheimer’s disease (AD) is an age-associated neurodegenerative disease and characterized by progressive loss of cognition and other neurobehavioral manifestations. Melatonin (N-acetyl-5-methoxytryptamine), a tryptophan metabolite and synthesized mainly in the pineal gland, has a number of physiological functions, including regulating circadian rhythms, clearing free radicals, improving immunity and generally inhibiting the oxidation of biomolecules. The level of melatonin in CSF decreases with the progression of AD neuropathology, as determined by the Braak stages [12]. Melatonin levels both in CSF and in postmortem human pineal gland are already reduced in preclinical AD subjects, who are cognitively still intact and have only the earliest signs of AD neuropathology [8,12]. From phenomenon observation to mechanism investigation and speculation
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