Neuroprotective effects of melatonin in neurodegenerative and autoimmune central nervous system diseases

Abstract

The suprachiasmatic nucleus (SCN) in the anterior hypothalamus is the major circadian pace-maker in humans. Melatonin is a key hormone secreted by the pineal gland in response to dark-ness. Light-induced stimuli are transmitted along the retinohypothalamic tract to the SCN. Acti-vation of the SCN inhibits the production of melatonin by the pineal gland through a complex neural pathway passing through the superior cervical ganglion. Accordingly, when light is una-vailable, the pineal gland secretes melatonin. The circadian rhythm modulates sleep-wake cycles as well as many physiological functions of the endocrine system, including core body tempera-ture, pulse rate, oxygen consumption, hormone levels, metabolism, and gastrointestinal function. In neurodegenerative disorders, the sleep-wake cycle is disrupted and circadian regulation is al-tered, which accelerates disease progression, further disrupting circadian regulation and setting up a vicious cycle. Melatonin plays a critical role in the regulation of circadian rhythms and is a multifunctional pleiotropic agent with broad neuroprotective effects in neurodegenerative disor-ders, viral or autoimmune diseases, and cancer. In this review, I discuss the neuroprotective functions of melatonin in circadian regulation and its roles in promoting anti-inflammatory activ-ity, enhancing immune system functions, and preventing alterations in glucose metabolism and mitochondrial dysfunction in neurodegenerative disorders and autoimmune central nervous sys-tem diseases.