Tumor necrosis factor-alpha regulates the Hypocretin system via mRNA degradation and ubiquitination

▶ The pro-inflammation cytokine, TNF-alpha, impairs the Hypocretin/Orexin system. ▶ TNF-alpha decreases the expression of Prepro-Hypocretin and Hypocretin receptor 2. ▶ TNF-alpha increases mRNA degradation and ubiquitination of the Hypocretin system. ▶ Impaired Hypocretin system contributes to the development of sleep disorders. ▶ TNF-alpha may regulate the sleep-wake cycle through the Hypocretin system.