Review abstract
Nature Chemical Biology 3, 630 - 639 (2007)
Published online: 17 September 2007 | doi:10.1038/nchembio.2007.37
Mammalian circadian signaling networks and therapeutic targets
Andrew C Liu1,2,3, Warren G Lewis1,2,3 & Steve A Kay1,3
Abstract
Virtually all cells in the body have an intracellular clockwork based on a negative feedback mechanism. The circadian timekeeping system in mammals is a hierarchical multi-oscillator network, with the suprachiasmatic nuclei (SCN) acting as the central pacemaker. The SCN synchronizes to daily light-dark cycles and coordinates rhythmic physiology and behavior. Synchronization in the SCN and at the organismal level is a key feature of the circadian clock system. In particular, intercellular coupling in the SCN synchronizes neuron oscillators and confers robustness against perturbations. Recent advances in our knowledge of and ability to manipulate circadian rhythms make available cell-based clock models, which lack strong coupling and are ideal for target discovery and chemical biology.
- Department of Biochemistry, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037, USA.
- Genomics Institute of the Novartis Research Foundation, 10675 John Jay Hopkins Drive, San Diego, California 92121, USA.
- Present address: Cell and Developmental Biology, University of California at San Diego, 9500 Gilman Drive, La Jolla, California 92093-0130, USA.
Correspondence to: Steve A Kay1,3 e-mail: stevek@scripps.edu
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