Role of melatonin in Alzheimer-like neurodegeneration

Alzheimer disease (AD),an age-related neurodegenerative disorder with progres-sive loss of memory and deterioration of comprehensive cognition,is character-ized by extracellular senile plaques of aggregated β-amyloid (Aβ),and intracellularneurofibrillary tangles that contain hyperphosphorylated tau protein.Recentstudies showed that melatonin,an indoleamine secreted by the pineal gland,mayplay an important role in aging and AD as an antioxidant and neuroprotector.Melatonin decreases during aging and patients with AD have a more profoundreduction in this hormone.Data from clinical trials indicate that melatonin supple-mentation improves sleep,ameliorates sundowning,and slows down the progres-sion of cognitive impairment in Alzheimer’s patients.Melatonin efficiently pro-tects neuronal cells from Aβ-mediated toxicity via antioxidant and anti-amyloidproperties:it not only inhibits Aβ generation,but also arrests the formation ofamyloid fibrils by a structure-dependent interaction with Aβ.Our recent studieshave demonstrated that melatonin efficiently attenuates Alzheimer-like tauhyperphosphorylation.Although the exact mechanism is still not fully understood,a direct regulatory influence of melatonin on the activities of protein kinases andprotein phosphatases is proposed.Additionally,melatonin also plays a role inprotecting cholinergic neurons and in anti-inflammation.Here,the neuroprotectiveeffects of melatonin and the underlying mechanisms by which it exerts its effectsare reviewed.The capacity of melatonin to prevent or ameliorate tau and Aβpathology further enhances its potential in the prevention or treatment of AD.