Circadian Rhythm Disruption in Parkinson's Disease
Circadian rhythms become disrupted with age. The maintenance of circadian rhythm is complex, and thus runs awry in complicated ways. For example, researchers have demonstrated an age-related mismatch between the activities of different circadian regulatory systems, leading to a growing contribution to age-related dysfunction in tissues. Researchers here review the evidence for disruption of circadian rhythm to specifically contribute to the progression of Parkinson's disease. In fact, there appears to be a bidirectional relationship between disrupted circadian rhythm and the pathology of Parkinson's disease.
Emerging evidence suggests that the circadian clock, the body's intrinsic timekeeping system, may play a critical role in the pathophysiology of Parkinson's disease (PD). Circadian rhythms (CR), which regulate a wide array of physiological processes, including sleep-wake cycles, hormone release, and metabolic functions, are disrupted in PD patients. This disruption not only exacerbates the motor and nonmotor symptoms of PD but may also influence the progression of neurodegeneration. Understanding the link between circadian rhythms and PD could reveal therapeutic strategies that align treatment with the body's natural rhythms, potentially improving outcomes and quality of life for patients.
Given the pervasive influence of circadian clocks on biological functions, optimizing the timing of pharmacological interventions, physical therapy, and lifestyle modifications in accordance with circadian rhythms could enhance treatment efficacy and mitigate side effects. In this review, we cover a wide range of potential medical-related applications of CR-spanning from its use as a biomarker, diagnostic or therapeutic approach while combining insights across cellular or animal models, and humans, with a particular focus on the PD field.
Molecular evidence also strongly links circadian clock dysfunction to neurodegeneration, particularly through disruptions in core clock genes (e.g., BMAL1 and PER2), and clock-controlled genes, which play critical roles in cellular homeostasis, mitochondrial function, and neuroinflammation. Furthermore, interventions to revert circadian changes, including bright light therapy or melatonin supplements, have shown promising benefits in improving both motor and nonmotor symptoms. Thus, if circadian disruption were purely a consequence of PD, the observed benefits of circadian-based interventions would be less likely, suggesting a bidirectional relationship where circadian dysfunction may, in addition, accelerate disease onset and or progression, as well as symptoms.