A Narrative Review: Suvorexant's Role in Sleep Deprivation and Neurodegenerative Disease

Sleep loss is a major risk factor for neurodegenerative diseases like Alzheimer's disease (AD) and Parkinson's disease (PD), accelerating cognitive impairment with neuropathology. Cumulative sleep loss impairs the glymphatic system, reduces amyloid-β clearance, and enhances the neuroinflammatory response, all of which contribute to the development of neurodegeneration. Given the orexin system's essential role in modulating sleep-wake rhythms, orexin receptor antagonists such as Suvorexant are potent candidates for treating sleep disturbances and cognitive decline associated with neurodegenerative conditions. Suvorexant promotes sustained sleep without the side effects commonly associated with sleep-inducing drugs, such as drowsiness and cognitive impairment, potentially offering a neuroprotective approach by selectively antagonizing orexin receptors. By inhibiting excessive orexin signaling in the brain, Suvorexant may benefit other neurodegenerative diseases. Preclinical studies support the idea that improving sleep quality, as seen with Suvorexant, can normalize sleep architecture, leading to reduced tau phosphorylation and amyloid plaque deposition, both of which are pathological hallmarks of AD. Furthermore, enhanced sleep quality may bolster synaptic plasticity and aid in memory consolidation, potentially counteracting cognitive deterioration. Although most research has been conducted in AD, the putative applications of Suvorexant in PD and other tauopathies are worth exploring, especially given the common involvement of sleep disturbances in these diseases. Animal studies show that Suvorexant not only promotes sleep but also prevents neuronal damage, suggesting its dual therapeutic potential. Long-term clinical trials are necessary, however, to prove its effectiveness in humans, especially in populations at risk for sleep disorders and early neurodegenerative alterations. Suvorexant could be a novel approach to slow cognitive decline and improve quality of life in patients with AD, PD, and related diseases, highlighting the vital interplay between sleep and brain health.