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 pacemaker in humans. Melatonin is a key hormone secreted by the pineal gland in response to darkness. Light-induced stimuli are transmitted along the retinohypothalamic tract to the SCN. Activation 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 unavailable, 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 temperature, pulse rate, oxygen consumption, hormone levels, metabolism, and gastrointestinal function. In neurodegenerative disorders, the sleep-wake cycle is disrupted and circadian regulation is altered, 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 disorders, 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 activity, enhancing immune system functions, and preventing alterations in glucose metabolism and mitochondrial dysfunction in neurodegenerative disorders and autoimmune central nervous system diseases.

Keywords: Autoimmune diseases of the nervous system; Circadian rhythm; Melatonin; Neurodegenerative diseases; Neuroprotection.

Figure 1.. Mechanisms on therapeutic targets of melatonin for neurodegenerative disorders and autoimmune CNS

ICAM, intracellular adhesion molecule; NF-κB, nuclear factor kappa B; IFN, interferon; Treg, T regulatory; Th, T helper; IL, interleukin; CNS, central nervous system disease.