How it works: The protein that stimulates muscle growth
Research findings may help identify drug targets for neuromuscular
disorders

Date:
April 27, 2022
Source:
University of Houston
Summary:
Using genetic approaches, researchers have demonstrated how a
certain protein is involved in skeletal muscle growth. The findings
open new avenues to develop drug targets for neuromuscular diseases
and other pathological conditions.



FULL STORY ==========================================================================
In the gym, you are not just pumping iron, you are oxygenating muscle
cells which keeps those muscles healthy, strong and growing -- a process
called hypertrophy, or an increase in muscle mass due to an increase in
muscle cell size. Conversely, under the covers, lounging, your muscles
may begin to atrophy, or shrink.


========================================================================== Scientists understand that a few signaling proteins are activated in
various conditions of muscle atrophy and hypertrophy, but they have been stumped about the role and mechanisms by which TAK1, a protein that
regulates innate immunity and the proinflammatory signaling pathways,
regulates skeletal muscle mass, until University of Houston researchers
began exploring.

"We demonstrate that supraphysiological activation of TAK1 in skeletal
muscle stimulates translational machinery, protein synthesis and myofiber growth," reports Ashok Kumar, UH College of Pharmacy Else and Philip
Hargrove Endowed Professor and chair, Department of Pharmacological and Pharmaceutical Sciences, in Nature Communications.

Using genetic approaches, Kumar and research assistant professor
Anirban Roy demonstrated that TAK1 is indispensable for maintaining
healthy neuromuscular junctions, which are involved in transmitting
nerve impulses to skeletal muscle and allow 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," said Roy.

Nutrients, growth hormones and weight training all result in an increase
in skeletal muscle mass in healthy individuals. Conversely, many disease conditions often lead to a loss in lean muscle mass. Understanding the mechanisms regulating protein and organelle content is highly important
to identify drug targets for various muscle wasting conditions and neuromuscular disorders.

The team also reports that activation of TAK1 in skeletal muscle beyond
normal levels can prevent excessive muscle loss due to nerve damage. Loss
of muscle mass has a devastating impact on standard-of-care treatment
during aging and terminal illnesses, such as cancer, COPD, kidney failure
and in many genetic neuromuscular diseases.

"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," said Roy.

Future studies will investigate whether the activation of TAK1 using small molecules is sufficient to promote muscle growth and prevent atrophy in
the elderly and various disease states.


========================================================================== Story Source: Materials provided by University_of_Houston. Original
written by Laurie Fickman. Note: Content may be edited for style and
length.


========================================================================== Journal Reference:
1. Anirban Roy, Ashok Kumar. Supraphysiological activation of TAK1
promotes
skeletal muscle growth and mitigates neurogenic atrophy. Nature
Communications, 2022; 13 (1) DOI: 10.1038/s41467-022-29752-0 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2022/04/220427115821.htm

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