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Molecular Links Between Circadian Rhythm Disruption, Melatonin, and Neurodegenerative Diseases: An Updated Review

Kemal Hüsnü Can Baser1, Ismail Celil Haskologlu2, Emine Erdag3

  • 1Department of Pharmacognosy, Faculty of Pharmacy, Near East University, 99138 Nicosia, Cyprus.

Molecules (Basel, Switzerland)
|May 14, 2025
PubMed

Insights

Circadian rhythms regulate bodily functions and are disrupted in neurodegenerative diseases. Melatonin and circadian-based therapies offer neuroprotection and potential treatments for these conditions.

Area of Science:

  • Neuroscience
  • Chronobiology
  • Molecular Biology

Background:

  • Circadian rhythms, governed by transcriptional-translational feedback loops (TTFLs), are crucial for physiological homeostasis.
  • Key regulators like CLOCK, BMAL1, PER, and CRY genes influence metabolism, oxidative balance, mitochondrial function, and synaptic plasticity.
  • Disruptions in circadian rhythms are implicated in the molecular pathophysiology of neurodegenerative diseases.

Purpose of the Study:

  • To review recent findings (past five years) on circadian dysregulation in neurodegeneration.
  • To highlight the molecular and cellular disturbances caused by circadian disruption.
  • To explore the translational potential of circadian-based therapies for neurodegenerative diseases.

Main Methods:

  • Literature review focusing on studies published within the last five years.
  • Analysis of research on clock gene expression and melatoninergic signaling in neurodegenerative disorders.
  • Examination of melatonin's role in modulating circadian rhythms, mitochondrial stability, and epigenetic/metabolic processes.

Main Results:

  • Circadian disruption contributes to the molecular pathophysiology of neurodegenerative disorders.
  • Altered clock gene expression and melatoninergic signaling may serve as early biomarkers.
  • Melatonin exhibits neuroprotective effects by influencing circadian pathways, mitochondrial function, and cellular stress responses.

Conclusions:

  • Circadian dysregulation is a significant factor in neurodegenerative disease development.
  • Melatonin and other circadian-based interventions hold promise for neuroprotection and therapeutic strategies.
  • Targeting circadian mechanisms offers a potential avenue for treating neurodegenerative conditions.
Keywords:
circadian rhythmclock genesmelatoninneurodegenerative diseases

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