Review article

Parkinson's disease and circadian rhythm disruption

Jelena Jakšić orcid.org/0000-0002-3520-296X ; School of Medicine, University of Zagreb, Zagreb, Croatia *

* Corresponding author.

Abstract

Parkinson’s disease (PD) is a progressive neurodegenerative disorder primarily associated with motor symptoms such as bradykinesia, rigidity, and tremor. However, it is increasingly recognized that non-motor symptoms—including sleep disturbances, mood disorders, cognitive impairment, and autonomic dysfunction are equally impactful and often precede the onset of motor signs. Mounting evidence highlights a strong bidirectional link between PD and circadian rhythm disruption. Circadian dysregulation is not only a consequence of PD- related neurodegeneration but also a potential contributing factor to its onset and progression. Central mechanisms underlying this interplay include dopamine (DA) dysregulation, microglial activation, and α-synuclein aggregation, all modulated by core circadian clock genes such as BMAL1, CLOCK, and REV-ERBα. Disruption of these genes impairs DA synthesis, promotes oxidative stress and inflammation, and accelerates neurodegeneration. Circadian dysfunction in PD also affects the suprachiasmatic nucleus and peripheral clocks, disrupting physiological rhythms governing sleep-wake cycles, thermoregulation, blood pressure, mood, gastrointestinal function, and urination. Notably, sleep disorders—particularly REM sleep behavior disorder (RBD), insomnia, and excessive daytime sleepiness, affect over 90% of PD patients and often appear in prodromal stages, offering a valuable opportunity for early diagnosis. RBD is considered one of the most specific predictors of future neurodegeneration, frequently preceding motor symptoms by more than a decade. Understanding the circadian regulation of DA transmission, immune function, and metabolic activity offers novel therapeutic avenues. Interventions aimed at restoring circadian rhythms, such as light therapy, melatonin supplementation, and pharmacological targeting of clock genes, have shown potential in alleviating both motor and non-motor symptoms and may modify disease progression. This growing recognition of the circadian system’s role in PD pathophysiology underscores the need for further research and integration of chronobiological strategies into personalized treatment plans.

Keywords

circadian rhythm; dopaminergic neurons; neurodegenerative diseases; Parkinson disease, sleep wake disorders

Hrčak ID:

343400

URI

https://hrcak.srce.hr/343400

Publication date:

28.12.2025.

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