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p38 MAPKs — roles in skeletal muscle physiology, disease mechanisms, and as potential therapeutic targets
Christopher M. Brennan, Charles P. Emerson Jr., Jane Owens, Nicolas Christoforou
Christopher M. Brennan, Charles P. Emerson Jr., Jane Owens, Nicolas Christoforou
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p38 MAPKs — roles in skeletal muscle physiology, disease mechanisms, and as potential therapeutic targets

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Abstract

p38 MAPKs play a central role in orchestrating the cellular response to stress and inflammation and in the regulation of myogenesis. Potent inhibitors of p38 MAPKs have been pursued as potential therapies for several disease indications due to their antiinflammatory properties, although none have been approved to date. Here, we provide a brief overview of p38 MAPKs, including their role in regulating myogenesis and their association with disease progression. Finally, we discuss targeting p38 MAPKs as a therapeutic approach for treating facioscapulohumeral muscular dystrophy and other muscular dystrophies by addressing multiple pathological mechanisms in skeletal muscle.

Authors

Christopher M. Brennan, Charles P. Emerson Jr., Jane Owens, Nicolas Christoforou

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Figure 2

Roles of p38 MAPK in myogenic differentiation and satellite cell function for regulation of the FSHD disease gene DUX4.

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Roles of p38 MAPK in myogenic differentiation and satellite cell functio...
Members of the p38 family of MAP kinases are activated in response to stress but also to a lesser extent in muscle cells by the myogenic differentiation program. p38α (MAPK14) and p38β (MAPK11) can be activated by 2 different MAP2Ks, MAP2K3 (MKK3) and MAP2K6 (MKK6). p38α and p38β have both been shown to have roles in regulation of satellite cell fate and myogenic differentiation; however, the use of inhibitors that are potent against both p38α and p38β in many studies makes discerning their roles independent of one another difficult. Examples of the role of p38α/β in regulation of myogenesis are illustrated here and discussed in more detail in the main text. Potential points of DUX4 regulation by p38 are indicated in red. Illustrated by Rachel Davidowitz.

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