Orexin-A
Orexin-A is a type of neuropeptide that plays a significant role in regulating sleep-wake cycles, appetite, and energy homeostasis. It is one of the two orexin peptides, the other being Orexin-B. Both are produced in the hypothalamus, a region of the brain that controls many bodily functions.
Structure and Function[edit | edit source]
Orexin-A is a 33-amino acid peptide that is highly conserved across species. It is produced by the prepro-orexin gene, which also produces Orexin-B. The orexin system consists of these two peptides and two G-protein coupled receptors, OX1R and OX2R. Orexin-A has equal affinity for both receptors, while Orexin-B preferentially binds to OX2R.
Orexin-A and Orexin-B are primarily produced by neurons in the lateral hypothalamus. These neurons project widely throughout the brain, allowing the orexins to regulate a variety of functions. The orexins are particularly important for maintaining wakefulness; loss of orexin-producing neurons is a cause of the sleep disorder narcolepsy.
Role in Sleep-Wake Regulation[edit | edit source]
Orexin-A plays a crucial role in the regulation of the sleep-wake cycle. It promotes wakefulness and inhibits REM sleep. In individuals with narcolepsy, a disorder characterized by excessive daytime sleepiness and cataplexy, there is a loss of orexin-producing neurons in the hypothalamus. This loss is thought to be the primary cause of the symptoms of narcolepsy.
Role in Appetite and Energy Homeostasis[edit | edit source]
In addition to its role in sleep regulation, Orexin-A also regulates appetite and energy homeostasis. It stimulates food intake and increases energy expenditure, contributing to the regulation of body weight. Orexin-A's role in energy homeostasis is thought to be mediated through its effects on the autonomic nervous system.
Clinical Significance[edit | edit source]
Given its role in sleep and energy homeostasis, Orexin-A is a potential target for the treatment of disorders such as narcolepsy, insomnia, and obesity. Several drugs that target the orexin system are currently in development or in clinical trials.
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