Chronopatho physiological implications of orexin in sleep disturbances and lifestyle-related disorders
Sleep, a mysterious behavior, has recently been recognized as a crucial factor for health and longevity. The daily sleep/wake cycle provides the basis of biorhythms controlling whole-body homeostasis and homeodynamics; therefore, disruption of sleep causes several physical and psychological disorders, including cardiovascular disease, obesity, diabetes, cancer, anxiety, depression, and cognitive dysfunction. However, the mechanism linking sleep disturbances and sleep-related disorders remains unknown. Orexin (also known as hypocretin) is a neuropeptide produced in the hypothalamus. Central levels of orexin #oscillate with the daily rhythm and peak at the awake phase. Orexin plays a major role in stabilizing the wakefulness state. Orexin deficiency causes sleep/wake-state instability, resulting in #narcolepsy. Hyper-activation of the orexin system also causes sleep disturbances, such as #insomnia, and hence, suvorexant, an orexin receptor #antagonist, has been clinically used to treat insomnia. Importantly, central actions of orexin regulate #motivated behaviors, stress response, and energy/glucose #metabolism by coordinating the central-autonomic nervous systems and #endocrine systems. These multiple actions of orexin maintain survival. However, it remains unknown whether chronopharmacological interventions targeting the orexin system ameliorate sleep-related disorders as well as sleep in humans. To understand the significance of adequate orexin action for #prevention of these disorders, this review summarizes the physiological functions of daily orexin action and pathological implications of its mistimed or reduced action in sleep disturbances and sleep-related disorders (#lifestyle-related physical and neurological disorders in particular). Timed administration of drugs targeting the orexin system may prevent lifestyle-related diseases by improving the quality of life (QOL) in #patients with sleep disturbances.
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https://doi.org/10.1016/j.pharmthera.2017.12.010
