Circadian disruption and its clinical implications in Parkinson's disease: A Narrative review.
Narrative review synthesizing molecular (clock genes, melatonin), neuropathological (SCN involvement, α-synuclein), animal and clinical evidence that circadian disruption contributes to motor and non-motor symptoms in Parkinson’s disease and summarizing interventions such as bright light therapy,…
What the AI sees
Narrative review synthesizing molecular (clock genes, melatonin), neuropathological (SCN involvement, α-synuclein), animal and clinical evidence that circadian disruption contributes to motor and non-motor symptoms in Parkinson’s disease and summarizing interventions such as bright light therapy,…
Research significance
Connects mechanistic circadian pathways to clinically actionable, low-risk interventions (light, melatonin, chronotherapy) and thereby highlights tractable targets and repurposing opportunities to improve sleep, nocturnal symptoms, and quality of life in PD, guiding translational and clinical trial…
Source abstract
This review integrates multiple levels of evidence, including molecular circadian mechanisms (e.g., clock genes and melatonin signaling), neuropathological findings (such as suprachiasmatic nucleus involvement and α-synuclein deposition), animal and human studies, clinical motor and non-motor symptomatology, and therapeutic interventions (including light therapy, melatonin, and chronotherapy). It provides a focused analysis of circadian dysfunction and related clinical manifestations in patients with Parkinson's disease (PD). Circadian disruption may result from pathological lesions affecting circadian regulation or a reduced neuronal firing rate in the central pacemaker. These alterations can modify circadian clock gene expression, such as BMAL1, and disrupt or shift melatonin secretion. Dopaminergic medications may also influence clock gene expression and melatonin rhythms. Circadian rhythm disorders in patients with PD may manifest as motor and non-motor symptoms, including sleep disorders, autonomic dysfunction, and depression. Therapeutic approaches include bright light therapy, melatonin and melatonin receptor agonists, and nonpharmacological strategies such as sleep hygiene, exercise, and chronotherapy. Although the genetic factors that cause circadian disruption have not been fully elucidated, and the underlying neuropathophysiology may differ because of overlapping circadian symptoms, each causative factor of sleep disorder in PD may be related to circadian rhythm disorders. Further studies to characterize the putative bidirectional relationship between sleep and circadian rhythms may help normalize sleep disorders and improve quality of life and nocturnal symptoms in patients with PD.