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Signalling pathways that mediate skeletal muscle hypertrophy and atrophy

Abstract

Atrophy of skeletal muscle is a serious consequence of numerous diseases, including cancer and AIDS. Successful treatments for skeletal muscle atrophy could either block protein degradation pathways activated during atrophy or stimulate protein synthesis pathways induced during skeletal muscle hypertrophy. This perspective will focus on the signalling pathways that control skeletal muscle atrophy and hypertrophy, including the recently identified ubiquitin ligases muscle RING finger 1 (MuRF1) and muscle atrophy F-box (MAFbx), as a basis to develop targets for pharmacologic intervention in muscle disease.

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Figure 1: Signalling pathways downstream of IGF-1.

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Acknowledgements

Thanks to L. S. Schleifer, P. R. Vagelos and G. D. Yancopoulos for enthusiastic support and critical guidance, and to the Regeneron community for their support. Thanks to colleagues at Procter & Gamble Pharmaceuticals for their support and for enthusiastic scientific collaboration, particularly R. Isfort. Particular thanks to G. Thurston for editing this manuscript. T. Stitt, M. Gonzalez, E. Latres, S. Stevens, M. Sleeman and K-L Lai also provided useful edits. Sincere apologies to scientific colleagues whose work was omitted from this perspective as a result of space constraints.

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Glass, D. Signalling pathways that mediate skeletal muscle hypertrophy and atrophy. Nat Cell Biol 5, 87–90 (2003). https://doi.org/10.1038/ncb0203-87

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