Chronotherapies for Parkinson's disease.

Parkinson's disease (PD) is the second-most common progressive neurodegenerative disorder. Although the clinical diagnosis of PD is still based on its cardinal motor dysfunctions, several non-motor symptoms (NMS) have been established as integral part of the disease. Unlike motor disorders, development of therapies against NMS are still challenging and remain a critical unmet clinical need. During the last decade, several studies have characterised the molecular, physiological and behavioural alterations of the circadian system in PD patients. As a consequence, and given the ubiquitous nature of circadian rhythms in the entire organism, the biological clock has emerged as a potential therapeutic target to ease suffering from both motor and NMS in PD patients. Here we discuss the emerging field of using bright light, physical exercise and melatonin as chronotherapeutic tools to alleviate motor disorders, sleep/wake alterations, anxiety and depression in PD patients. We also highlight the potential of these readily available therapies to improve the general quality of life and wellbeing of PD patients. Finally, we provide specific data- and mechanisms-driven recommendations that might help improve the therapeutic benefit of light and physical exercise in PD patients.