Targeting sleep and the circadian system as a novel treatment strategy for Parkinson’s disease

• Published in: Journal of neurology Vol. 271; no. 3; pp. 1483 - 1491
• Main Authors: Feigl, Beatrix, Lewis, Simon J. G., Rawashdeh, Oliver
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 01.03.2024; Springer Nature B.V
• Subjects: Brain research; Circadian rhythm; Circadian Rhythm - physiology; Circadian rhythms; Disorders of Excessive Somnolence - etiology; Humans; Light; Medicine; Medicine & Public Health; Melatonin; Movement disorders; Neural networks; Neurodegeneration; Neurodegenerative diseases; Neurological Update; Neurology; Neuropathology; Neuroradiology; Neurosciences; Orexins; Pacemakers; Parkinson Disease - complications; Parkinson Disease - diagnosis; Parkinson Disease - therapy; Parkinson's disease; Photoreceptors; Precision medicine; Quality of Life; Sleep; Sleep - physiology; Sleep and wakefulness; Sleep Initiation and Maintenance Disorders; Sleep Wake Disorders - etiology; Sleep Wake Disorders - therapy; Disease modifying Therapy; Chronobiology; Neurodegeneration; Photoreceptor; Small molecule; Circadian; Orexin
• ISSN: 0340-5354; 1432-1459
• DOI: 10.1007/s00415-023-12073-7

There is a growing appreciation of the wide range of sleep–wake disturbances that occur frequently in Parkinson’s disease. These are known to be associated with a range of motor and non-motor symptoms and significantly impact not only on the quality of life of the patient, but also on their bed partner. The underlying causes for fragmented sleep and daytime somnolence are no doubt multifactorial but there is clear evidence for circadian disruption in Parkinson’s disease. This appears to be occurring not only as a result of the neuropathological changes that occur across a distributed neural network, but even down to the cellular level. Such observations indicate that circadian changes may in fact be a driver of neurodegeneration, as well as a cause for some of the sleep–wake symptoms observed in Parkinson’s disease. Thus, efforts are now required to evaluate approaches including the prescription of precision medicine to modulate photoreceptor activation ratios that reflect daylight inputs to the circadian pacemaker, the use of small molecules to target clock genes, the manipulation of orexin pathways that could help restore the circadian system, to offer novel symptomatic and novel disease modifying strategies.