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Sleep and circadian rhythms in α-synucleinopathies-Perspectives for disease modification
Dieter Kunz1,2, Henrik Oster3, Oliver Rawashdeh4
1Institute of Physiology, Sleep Research & Clinical Chronobiology, Charité - Universitätsmedizin Berlin, Berlin, Germany.
Acta Physiologica (Oxford, England)
|March 23, 2023
Summary
Neurodegenerative diseases like Parkinson's are rising. This review explores how disrupted circadian rhythms and sleep, particularly in isolated REM sleep behavior disorder (iRBD), contribute to these conditions, offering therapeutic insights.
Area of Science:
- Neuroscience
- Chronobiology
- Neurology
Background:
- Rising prevalence of neurodegenerative diseases, including Parkinson's disease, in the Global North.
- While lifestyle factors are implicated, they don't fully explain the surge in neurodegeneration.
- Circadian rhythm and sleep disruption are increasingly recognized as critical factors in neurodegeneration pathogenesis.
Purpose of the Study:
- To review current knowledge on sleep and circadian rhythm disruptions in alpha-synucleinopathies.
- To emphasize the molecular aspects and therapeutic potentials related to these disruptions.
- To highlight isolated REM sleep behavior disorder (iRBD) as a prodromal state for insights into early disease development.
Main Methods:
- Review of existing literature on sleep, circadian rhythms, and alpha-synucleinopathies.
- Focus on molecular mechanisms underlying circadian timekeeping and their role in neurodegeneration.
- Exploration of experimental and clinical approaches to study these phenomena.
Main Results:
- Sleep and circadian rhythm disruptions are implicated in the early stages of neurodegeneration.
- Isolated REM sleep behavior disorder (iRBD) serves as a prodromal marker for Parkinson's disease and related disorders.
- Specific circadian abnormalities in iRBD require further investigation despite REM sleep's strong circadian modulation.
Conclusions:
- Understanding circadian and sleep disruptions is crucial for unraveling neurodegenerative disease pathogenesis.
- Targeting the disturbed circadian system early in disease may offer novel therapeutic interventions.
- Further research into molecular circuitry of circadian timekeeping can provide insights into alpha-synucleinopathies.
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