Circadian clock disruption and neuroinflammation in Parkinson's disease: a new perspective

Disturbance of the circadian system is one of the most common non-motor symptoms in Parkinson's disease (PD) patients and often precedes the onset of the disease by many years. For decades, sleep disorders have mainly been considered a consequence of the neuropathology. However, research suggests that circadian disruption might actually contribute to the neurodegenerative process by dysregulating the immune system function. Chronic inflammation is known to be a crucial component of PD neuropathology. In fact, excessive activation of the inflammatory response and increased levels of proinflammatory mediators in the substantia nigra render dopaminergic neurons more vulnerable to neurodegenerative insults. Thus, animal and longitudinal studies with human patients have unraveled the existence of a strong bidirectional relation between circadian clock disturbances and inflammation suggesting that treatment of sleeping disorders could be a way to delay the onset and/or development of PD. This chapter will focus on the biologic evidence linking circadian system disruption, sleep disorders, and inflammation in the pathophysiology of PD.