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The 2017 Nobel Prize in Physiology or Medicine was awarded to Jeffrey C. Hall, Michael Rosbash and Michael W. Young for their elucidation of the molecular mechanisms controlling circadian rhythm. Their pioneering work in Drosophila uncovered the internal oscillators, or clocks, that synchronise cellular metabolism and organismal behaviour to the light/dark cycle to generate biological rhythms with 24 hour periodicity.
The circadian clock plays a central part in the regulation of liver function. In this Review, Tahara and Shibata discuss the mechanisms by which the circadian clock controls hepatic metabolism and the processing of xenobiotics, and how clock dysfunction can influence liver disease.
This perspective discusses the role of epigenetic mechanisms in regulating circadian rhythms, and emphasizes that the role of peripheral machinery is key for a fuller understanding of this regulation.
Clock proteins are controlled by multiple post-translational modifications during the circadian cycle. In this Review, the authors examine how post-translational modifications influence the stability, interactions and activity of mammalian clock proteins and how they contribute to proper clock function or are altered in circadian disorders.
What is the driving force behind periodic biological oscillations such as the circadian, hibernation and sleep–wake cycles? Temporal compartmentalization of metabolism has been shown in budding yeast, and might form the underlying basis for many of the rhythmic phenomena in biology.
Circadian rhythms are well established as having an important role in human biology. In this Review, circadian biology is presented in reference to the regulation of rheumatoid arthritis and the potential for chronotherapeutic intervention.
Evidence indicates that the disruption of the circadian clock might be directly linked to cancer. As described here, alterations in clock function could lead to aberrant cellular proliferation, DNA damage responses and altered metabolism.
Disruption of circadian rhythms in neurodegenerative disorders not only contributes to morbidity and poor quality of life, but could also be involved in driving the disease process itself. Restoration of circadian rhythmicity via behavioural or pharmacological interventions might, therefore, slow down disease progression. In this Review, Videnovic and colleagues provide an overview of the circadian system, and summarize current understanding of the dysfunction of circadian rhythms in Alzheimer disease, Parkinson disease and Huntington disease.
Adequate circadian oscillation of endocrine factors is essential in the maintenance of metabolic homeostasis. The authors of this Review explain the influence of extrinsic and intrinsic factors on endocrine circadian rhythms and how dysregulation of these rhythms can lead to disease in animals and humans. They also discuss therapeutic strategies to restore circadian rhythmicity and improve metabolism.