Epigenetic drugs in the treatment of skeletal muscle atrophy.
OBJECTIVE
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.


RESULTS
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.


CONCLUSIONS
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.
Guasconi
Valentina
V
Dulbecco Telethon Institute (DTI) at Fondazione Santa Lucia/EBRI, Rome, Italy.
Puri
Pier Lorenzo
PL
D044127:Epigenesis, Genetic; D005786:Gene Expression Regulation; D015316:Genetic Therapy; D006801:Humans; D009124:Muscle Proteins / Q000096:biosynthesis; D018482:Muscle, Skeletal / Q000201:enzymology / Q000378:metabolism*; D009133:Muscular Atrophy / Q000517:prevention & control / Q000628:therapy*; D015398:Signal Transduction; D014158:Transcription, Genetic
D009124:Muscle Proteins