Biochemical Mechanisms of Sleep Regulation

Sleep is a highly orchestrated neurophysiological process governed by intricate biochemical pathways involving neurotransmitters and hormones that modulate sleep architecture and circadian rhythmicity. This review presents a comprehensive synthesis of current molecular insights into the regulatory mechanisms of sleep, with a particular focus on the roles of γ-aminobutyric acid (GABA), serotonin, adenosine, acetylcholine, and norepinephrine in sleep stage modulation. It further explores the circadian and homeostatic functions of hormones, including melatonin, cortisol, orexins, leptin, and ghrelin, highlighting their integrative roles in linking neural circuitry with systemic physiological states. The article delineates how disruptions in these pathways underpin major sleep disorders, such as insomnia, narcolepsy, obstructive sleep apnea, restless leg syndrome, and circadian rhythm sleep-wake disorders, through mechanisms ranging from GABAergic deficits and HPA axis hyperactivation to orexin deficiency and clock gene dysregulation. By bridging neurochemical theory with clinical pathology, the review underscores the translational potential of targeting neuroendocrine circuits for therapeutic intervention. The findings advocate for the advancement of personalized sleep medicine through molecular diagnostics and emphasize the importance of circadian coherence in neurodegenerative and metabolic disease management. Collectively, this work consolidates multidisciplinary evidence into a cohesive framework, contributing to the evolving paradigm of sleep biology and its clinical relevance.