Researchers discover protein that enhances muscle mass

Humans are not just pumping iron in the gym, or not just oxygenating muscle cells, which keeps those muscles healthy, powerful, and developing—a process known as hypertrophy—that is defined as an increase in muscle mass, caused by an increase in muscle cell size. On the other hand, if people spend too much time beneath the covers, the muscles may tend to atrophy or shrink.

Researchers discover protein that enhances muscle mass
Ashok Kumar, UH College of Pharmacy Else and Philip Hargrove Endowed Professor and Chair, Department of Pharmacological and Pharmaceutical Sciences, and research assistant professor Anirban Roy are reporting that inactivation of the TAK1 protein causes derangement of neuromuscular junctions and severe muscle wasting. Image Credit: University of Houston

Researchers have determined that a few signaling proteins are stimulated in different conditions of muscle atrophy and hypertrophy, but they had no idea how TAK1, a protein that controls innate immunity and pro-inflammatory signaling pathways, governs skeletal muscle mass until University of Houston researchers started looking into it.

We demonstrate that supraphysiological activation of TAK1 in skeletal muscle stimulates translational machinery, protein synthesis, and myofiber growth.”

Ashok Kumar, College of Pharmacy, University of Houston

Kumar was also the Else and Philip Hargrove Endowed Professor and Chair, at the Department of Pharmacological and Pharmaceutical Sciences. The study was reported in the journal Nature Communications.

Kumar and research assistant professor Anirban Roy used genetic techniques to show that TAK1 is required for keeping healthy neuromuscular junctions, which carry nerve signals to skeletal muscle and enable muscle contractions.

Our findings demonstrate that targeted inactivation of TAK1 causes derangement of neuromuscular junctions and severe muscle wasting, very similar to muscle wasting observed during nerve damage, aging, and cancer cachexia. We have also identified a novel interplay between TAK1 and BMP (Bone Morphogenetic Protein) signaling pathway that promotes muscle growth.”

Anirban Roy, Research Assistant Professor, University Of Houston

In healthy people, nutrients, growth hormones, and weight training all contribute to a boost in skeletal muscle mass. On the other hand, several diseases cause a loss of lean muscle mass. Insights into the mechanisms that control protein and organelle composition are critical for identifying therapeutic targets for muscle atrophy and neuromuscular diseases.

TAK1 activation above normal levels in skeletal muscle can also help prevent muscle loss owing to nerve injury, according to the researchers. Muscle loss during aging and severe illnesses such as cancer, COPD, kidney failure, and many hereditary neuromuscular diseases has a catastrophic impact on conventional treatments.

Recognizing the impact of TAK1 signaling in supporting muscle growth, our research opens up new avenues to develop therapies for these and many other pathological conditions and improve quality of life.”

Anirban Roy, Research Assistant Professor, University Of Houston

Future research will look at whether small-molecule activation of TAK1 is enough to stimulate muscle growth and avoid atrophy in the elderly and multiple disease conditions.

Source:
Journal reference:

Roy, A., & Kumar, A. (2022) Supraphysiological activation of TAK1 promotes skeletal muscle growth and mitigates neurogenic atrophy. Nature Communications. doi.org/10.1038/s41467-022-29752-0.

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