Melatonin signaling as a link between sleep and circadian biology: practical implications

CARDINALI DP; BROWN GM

Synopsis of Sleep Medicine

Apple Academic Press

Año: 2017; p. 119 - 145

Normal circadian rhythms are cynchronized to aregular 24 h environmental light-dark cycle. Both the suprachiasmatic nucleus(SCN) and melatonin are essential for this adaptation. Melatonin exerts itschronophysiological action in part by acting through specific membranereceptors (MT1, MT2) which have been identified in SCN cells as well as inseveral neural and non-neural tissues. Both receptors have been cloned and sharegeneral features with other G protein linked receptors. Melatonn also exertsdirect effects on intracellular proteins, such as calmodulin or tubulin, hasstrong free radical scavenger properties, with are non-receptor mediated, is aneffective mitochondrial protector and may interact with proteasome to affectintracellular physiology. Within the SCN melatonin reduces neuronal activity ina time-dependent manner. The disruption of these circadian mechanisms causes anumber of sleep disorders known as circadian rhythm sleep disorders (CRSDs).CRSDs include delayed or advanced sleep phase syndromes, non-24 h sleep-wakerhythm disorder, time zone change syndrome (?jet lag?) and shift work sleepdisorder. Disturbances in circadian phase position of plasma melatonin levelshave been found in all these disorders. Inn addition, comorbidity of severecircadian alterations with neurodegenerative diseases like Alzheimer´sdisease  (AD) has been documented,Currently there is sufficient evidence to implicate endogenousmelatonin as animportant mediator in CRSD pathophysiology. The documented efficacy ofmelatonin to reduce chronic benzodiazepine/Z drug use in insomnia patients inalso discussed