Epigenetic drugs in the treatment of skeletal muscle atrophy.

Anabolic and catabolic signals Current Opinion in Clinical Nutrition & Metabolic Care. 11(3):233-241, May 2008.
Guasconi, Valentina a; Puri, Pier Lorenzo a,b

Abstract:
Purpose of review: A dynamic network of anabolic and catabolic pathways regulates skeletal muscle mass in adult organisms. Muscle atrophy is the detrimental outcome of an imbalance of this network. The purpose of this review is to provide a critical evaluation of different forms of muscle atrophy from a mechanistic and therapeutic point of view.

Recent findings: The identification and molecular characterization of distinct pathways implicated in the pathogenesis of muscle atrophy have revealed potential targets for therapeutic interventions. However, an effective application of these therapies requires a better understanding of the relative contribution of these pathways to the development of muscle atrophy in distinct pathological conditions.

Summary: We propose that the decline in anabolic signals (’passive atrophy’) and activation of catabolic pathways (’active atrophy’) contribute differently to the pathogenesis of muscle atrophy associated with distinct diseases or unfavorable conditions. Interestingly, these pathways might converge on common transcriptional effectors, suggesting that an optimal intervention should be directed to targets at the chromatin level. We provide the rationale for the use of epigenetic drugs such as deacetylase inhibitors, which target multiple signaling pathways implicated in the pathogenesis of muscle atrophy.

(C) 2008 Lippincott Williams & Wilkins, Inc.

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