Author(s)

Peiyun Huang, Ziyao Wu

Corresponding Author

Ziyao Wu

ABSTRACT

The disorder of sleep and rhythm has long been considered as the pathological manifestations of Alzheimer's disease (AD). The growing evidence has been showing the potential relationship between sleep and circadian rhythm regulations with the occurrence and development of AD. Therefore, it is crucial to improve sleep and circadian rhythms. Melatonin, a hormone secreted by the pineal gland, plays an important role in regulating human sleep and circadian rhythm. A potential mechanism is that melatonin improves sleep and rhythm disorders, and thus, indirectly regulates the pathogenesis of AD. Moreover, the pathogenesis of AD includes free radical oxidative damage, as well as neuroinflammation. In recent years, many studies have proved neuroendocrine immunomodulatory activity and free radical scavenging antioxidant capacity of melatonin. As a free radical scavenger, melatonin participates in the antioxidant system and regulates the symptoms of AD. This review summarizes signaling pathways leading to the pathogenesis of AD, such as neuroinflammation, Aβ burden and increasing Tau level. Apart from pathogenesis of AD, effects of melatonin on the regulation of clock genes and the role of its receptors MT1 and MT2 in improving sleep disorders and circadian rhythm deterioration are discussed. Clinical trials show melatonin may also improve the cognitive ability of AD patients. This review attempts to provide a broader perspective and new direction for prevention and treatment of AD with melatonin.

KEYWORDS

Melatonin, Sleep and Circadian Rhythms, Alzheimer’s Disease, Clock Gene