The circadian system in Parkinson's disease, multiple system atrophy, and progressive supranuclear palsy

Circadian organization of physiology and behavior is an important biologic process that allows organisms to anticipate and prepare for predictable changes in the environment. Circadian disruptions are associated with a wide range of health issues. In patients with neurodegenerative diseases, alterations of circadian rhythms are among the most common and debilitating symptoms. Although a growing awareness of these symptoms has occurred during the last decade, their underlying neuropathophysiologic circuitry remains poorly understood and, consequently, no effective therapeutic strategies are available to alleviate these health issues. Recent studies have examined the neuropathologic status of the different neural components of the circuitry governing the generation of circadian rhythms in neurodegenerative diseases. In this review, we will dissect the potential contribution of dysfunctions in the different nodes of this circuitry to circadian alterations in patients with parkinsonism-linked neurodegenerative diseases (namely, Parkinson's disease, multiple system atrophy, and progressive supranuclear palsy). A deeper understanding of these mechanisms will provide not only a better understanding of disease neuropathophysiology but also holds promise for the development of more effective and mechanisms-based therapies.