<p>The Circadian System is a complex network of coordinated clocks that regulates the organism’s internal clock in synchronisation with the outside world. These rhythms are controlled by genetically controlled positive and negative transcriptional-translational feedback loops (TTFL) that generate 24-hour oscillations in the protein level and mRNA of core circadian components. Circadian disruption is recognised as a significant contributor to the molecular pathogenesis of neurodegenerative illnesses, as disease-specific alterations in clock gene expression and melatoninergic signalling have been identified as possible early-stage molecular indicators. Emerging evidence suggests a link between dysregulated circadian rhythms and neurodegenerative diseases, implying that the changes in circadian function may play a critical role in the development and progression of neurodegenerative diseases. The correlation between circadian rhythm and neurodegeneration is highly promising for developing treatment and promoting healthy lifestyle measures. This review article primarily focuses on how abnormalities in circadian rhythms may increase the risk of neurodegenerative diseases, including Alzheimer’s disease (AD), Parkinson’s disease (PD), Huntington’s disease (HD), and Amyotrophic Lateral Sclerosis (ALS). Applying knowledge from pre-clinical and translational research on neurodegenerative diseases is crucial for lowering the risks of neurodegeneration and improving the symptoms and quality of life of people with neurodegenerative diseases through approaches that restore circadian rhythm in the context of precision medicine. Understanding this interaction holds promise for developing therapeutic approaches to support a healthy lifestyle.</p>

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Circadian disruption as a driver and target in neurodegenerative diseases: from molecular mechanisms to chronotherapeutic strategies

  • Atulit Maidh,
  • Palak Kalra,
  • Heena Khan,
  • Pragati Silakari,
  • Amarjot Kaur Grewal

摘要

The Circadian System is a complex network of coordinated clocks that regulates the organism’s internal clock in synchronisation with the outside world. These rhythms are controlled by genetically controlled positive and negative transcriptional-translational feedback loops (TTFL) that generate 24-hour oscillations in the protein level and mRNA of core circadian components. Circadian disruption is recognised as a significant contributor to the molecular pathogenesis of neurodegenerative illnesses, as disease-specific alterations in clock gene expression and melatoninergic signalling have been identified as possible early-stage molecular indicators. Emerging evidence suggests a link between dysregulated circadian rhythms and neurodegenerative diseases, implying that the changes in circadian function may play a critical role in the development and progression of neurodegenerative diseases. The correlation between circadian rhythm and neurodegeneration is highly promising for developing treatment and promoting healthy lifestyle measures. This review article primarily focuses on how abnormalities in circadian rhythms may increase the risk of neurodegenerative diseases, including Alzheimer’s disease (AD), Parkinson’s disease (PD), Huntington’s disease (HD), and Amyotrophic Lateral Sclerosis (ALS). Applying knowledge from pre-clinical and translational research on neurodegenerative diseases is crucial for lowering the risks of neurodegeneration and improving the symptoms and quality of life of people with neurodegenerative diseases through approaches that restore circadian rhythm in the context of precision medicine. Understanding this interaction holds promise for developing therapeutic approaches to support a healthy lifestyle.