Fig. 1.

Possible mechanisms of interplay between circadian and sleep dysfunctions and Parkinson’s disease. The suprachiasmatic nucleus (SCN) acts as the central circadian pacemaker, coordinating peripheral clocks, and assisting in the establishment and maintenance of sleep (through process C), which is also contributed by other factors (process S). The SCN uses molecular mechanisms to generate circadian rhythmicity, with zeitgebers (most importantly light) fine-tuning the rhythm. Sleep dysfunction can disrupt these rhythms. Dysfunction of sleep and of peripheral clocks, such as those in microglial and neuronal cells, leads to subsequent changes within and outside of the brain, including neuroinflammation, increased oxidative stress and reduced metabolic clearance. These outcomes have been proposed to increase risk of Parkinson’s disease onset, and to exacerbate Parkinson’s disease progression. Resultant neurodegeneration due to Parkinson’s disease can negatively affect neural pathways, and subsequently desynchronize (or ‘break’) the clock, contributing to a self-perpetuating loop. Parkinson’s disease is also associated with several sleep disorders, negatively impacting sleep and further contributing to the two-way interplay between circadian rhythms and neurodegeneration