AI Article Synopsis
- Chronic disruptions to our circadian rhythms, often caused by shift work or traveling across time zones, can lead to health issues like diabetes, cardiovascular disease, and cancer.
- Researchers conducted a chemical screening of existing drugs to find potential new treatments for circadian disorders, identifying about 5% that influenced circadian rhythms, particularly noting the compound DHEA which can shorten the circadian period and lessen jet-lag effects.
- The study also highlighted the role of specific kinases (ABL1, ABL2, and BCR) in regulating circadian rhythms, showing that repurposing known drugs could be a promising strategy for developing therapies for circadian-related health issues.
Article Abstract
Chronic circadian disruption due to shift work or frequent travel across time zones leads to jet-lag and an increased risk of diabetes, cardiovascular disease, and cancer. The development of new pharmaceuticals to treat circadian disorders, however, is costly and hugely time-consuming. We therefore performed a high-throughput chemical screen of existing drugs for circadian clock modulators in human U2OS cells, with the aim of repurposing known bioactive compounds. Approximately 5% of the drugs screened altered circadian period, including the period-shortening compound dehydroepiandrosterone (DHEA; also known as prasterone). DHEA is one of the most abundant circulating steroid hormones in humans and is available as a dietary supplement in the USA Dietary administration of DHEA to mice shortened free-running circadian period and accelerated re-entrainment to advanced light-dark (LD) cycles, thereby reducing jet-lag. Our drug screen also revealed the involvement of tyrosine kinases, ABL1 and ABL2, and the BCR serine/threonine kinase in regulating circadian period. Thus, drug repurposing is a useful approach to identify new circadian clock modulators and potential therapies for circadian disorders.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5938619 | PMC |
| http://dx.doi.org/10.15252/emmm.201708724 | DOI Listing |
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