Chronobiology of Parkinson's disease: Past, present and future

• Published in: The European journal of neuroscience Vol. 57; no. 1; pp. 178 - 200
• Main Authors: Asadpoordezaki, Ziba, Coogan, Andrew N., Henley, Beverley M.
• Format: Journal Article
• Language: English
• Published: France Wiley Subscription Services, Inc 01-01-2023; John Wiley and Sons Inc
• Subjects: Chronobiology Disorders - complications; chronotherapy; circadian clocks; Circadian rhythm; Circadian Rhythm - physiology; Circadian rhythms; Clinical and Translational Neuroscience; Dopamine receptors; Humans; Levodopa; Mesencephalon; Molecular modelling; Movement disorders; Neurodegenerative Diseases; Parkinson Disease; Parkinson's disease; Precision medicine; Quality of Life; Review; Sleep; Sleep - physiology; sleep–wake disorders; neurodegenerative diseases; chronotherapy; Parkinson's disease; circadian clocks; sleep-wake disorders; circadian rhythm
• ISSN: 0953-816X; 1460-9568
• DOI: 10.1111/ejn.15859

Parkinson's disease is a neurodegenerative disorder predominately affecting midbrain dopaminergic neurons that results in a broad range of motor and non‐motor symptoms. Sleep complaints are among the most common non‐motor symptoms, even in the prodromal period. Sleep alterations in Parkinson's disease patients may be associated with dysregulation of circadian rhythms, intrinsic 24‐h cycles that control essential physiological functions, or with side effects from levodopa medication and physical and mental health challenges. The impact of circadian dysregulation on sleep disturbances in Parkinson's disease is not fully understood; as such, we review the systems, cellular and molecular mechanisms that may underlie circadian perturbations in Parkinson's disease. We also discuss the potential benefits of chronobiology‐based personalized medicine in the management of Parkinson's disease both in terms of behavioural and pharmacological interventions. We propose that a fuller understanding of circadian clock function may shed important new light on the aetiology and symptomatology of the disease and may allow for improvements in the quality of life for the millions of people with Parkinson's disease.
In Parkinson's disease, pathological α‐synuclein aggregation and Lewy body formation may lead to the death of dopaminergic neurons, which has a bi‐directional influence on circadian rhythm dysfunction and sleep disturbances. L‐dopa treatment and dopamine agonists may also influence circadian rhythm dysfunction. Sleep disturbances such as social jet lag/shift work can have a bi‐directional influence on circadian rhythm dysfunction.