Targeting the orexin/hypocretin system for the treatment of neuropsychiatric and neurodegenerative diseases: From animal to clinical studies
Source : https://www.sciencedirect.com/science/article/pii/S0091302223000146?via=ihub
Orexins (also known as hypocretins) are neuropeptides located exclusively in hypothalamic neurons that have extensive projections throughout the centr...
Summary: Orexins progressively decline during PD and this may contribute to some clinical manifestations of the disease, such as excessive daytime sleepiness. In addition, since orexins play a neuroprotective function over nigral dopaminergic neurons, deficient orexinergic transmission in turn may worsen disease severity and progression. As shown in preclinical models, orexin replacement therapy could potentially attenuate both motor and non-motor clinical manifestations of PD and delay disease progression.
• Source: Frontiers in Neuroendocrinology
• Conclusions: “In this review, we discuss and update the main preclinical and human studies involving the orexin system with several psychiatric and neurodegenerative diseases. This system constitutes a nice example of how basic scientific research driven by curiosity can be the best route to the generation of new and powerful pharmacological treatments.”
• Orexins were originally known for their role in feeding and arousal. Today, they are recognized as important in different physiological and pathological conditions.
• Three receptor antagonists—suvorexant, lemborexant and daridorexane—are approved by the FDA for the treatment of insomnia
• “Lemborexant and daridorexant are DORAs [dual orexin receptor antagonists] also approved by the FDA for the treatment of insomnia disorder. Unlike GABAA receptor modulators, DORAs promote NREM and REM sleep, do not disrupt sleep stage-specific quantitative electroencephalogram spectral profiles, and allow somnolence indistinct from normal sleep. The preservation of cognitive performance and the ability to arouse to salient stimuli after DORA administration suggest further advantages over historical therapies,” the authors wrote.
• The orexin system is disturbed in stress related disorders and neurogenerative diseases. Activation of the orexin system could treat narcolepsy, Parkinson disease, and major depressive disorder. On the other hand blockade of the orexin system could treat anxiety, fear-related disorders, eating disorders, and Alzheimer disease.