AUTHOR=Yang Zhengjie, Zhang Xiaona, Li Chengqian, Chi Song, Xie Anmu TITLE=Molecular Mechanisms Underlying Reciprocal Interactions Between Sleep Disorders and Parkinson’s Disease JOURNAL=Frontiers in Neuroscience VOLUME=14 YEAR=2021 URL=https://www.frontiersin.org/articles/10.3389/fnins.2020.592989 DOI=10.3389/fnins.2020.592989 ISSN=1662-453X ABSTRACT=Sleep–wake disruptions are among the most prevalent and burdensome non-motor symptoms of Parkinson’s disease (PD). Clinical studies have demonstrated that these disturbances can precede the onset of typical motor symptoms by years, indicating that they may play a primary function in the pathogenesis of PD. Animal studies suggest that sleep facilitates the removal of metabolic wastes through the glymphatic system via convective flow from the periarterial space to the perivenous space, upregulates antioxidative defenses, and promotes the maintenance of neuronal protein homeostasis. Therefore, disruptions to the sleep–wake cycle have been associated with inefficient metabolic clearance and increased oxidative stress in the central nervous system (CNS). This leads to excessive accumulation of alpha-synuclein and the induction of neuronal loss, both of which have been proposed to be contributing factors to the pathogenesis and progression of PD. Additionally, recent studies have suggested that PD-related pathophysiological alterations during the prodromal phase disrupt sleep and circadian rhythms. Taken together, these findings indicate potential mechanistic interactions between sleep–wake disorders and PD progression as proposed in this review. Further research into the hypothetical mechanisms underlying these interactions would be valuable, as positive findings may provide promising insights into novel therapeutic interventions for PD.