Study identifies protein important for motor coordination and exercise performance

Date:
September 29, 2021
Source:
Karolinska Institutet
Summary:
Researchers have identified a protein that improves muscular
metabolism, motor coordination and exercise performance in mice. The
findings could be of therapeutic value for patients with muscle
and neurological diseases, such as ALS.



FULL STORY ========================================================================== Researchers at Karolinska Institutet in Sweden have identified a protein
that improves muscular metabolism, motor coordination and exercise
performance in mice. The findings, published in Cell Metabolism, could be
of therapeutic value for patients with muscle and neurological diseases,
such as ALS.


========================================================================== Muscle health is a major determinant of overall health and the best
way to keep muscles healthy is to exercise regularly. However, for some patients with debilitating diseases, exercise is not always possible. For
that reason, researchers are looking for molecules that can by themselves
bring about some of the benefits of physical exercise.

In the current study, researchers at Karolinska Institutet wanted to
know how a muscle-produced protein called neurturin affects neuromuscular function.

Understanding what signals mediate motor neuron and muscle communication
is essential for exploring new treatments for muscle-related and
neurological diseases, such as amyotrophic lateral sclerosis (ALS).

"We wanted to know if muscles can talk back to motor neurons by sending
their own messages, and to find out what are the consequences of those signals," says Jorge Ruas, professor at the Department of Physiology
and Pharmacology, Karolinska Institutet, and corresponding author.

The researchers found that mice that were genetically modified to
produce more neurturin in muscle cells significantly improved their
muscle metabolism, exercise performance and motor coordination compared
to regular mice. The high neurturin mice also had an increased number
of motor neurons of a type that is more resistant to degeneration in
diseases like ALS.

"To find out that a molecule released from muscle fibres can actually
change motor neuron identity, shifting them to a type that is associated
with more resistance to degeneration opens really exciting possibilities
for the future," Jorge Ruas adds.

As a next step, the researchers are hoping to explore the therapeutic possibilities of neurturin in mouse models of type 2 diabetes, obesity
and ALS.

They are also working on modifying the administration of neurturin to
allow it to be used as a potential drug.

"There's much to be done, but we believe this could be of therapeutic
value for patients with metabolic and neuromuscular diseases, such as
type 2 diabetes and ALS," says the study's first author Jorge Correia, researcher at the Department of Physiology and Pharmacology, Karolinska Institutet.

The researchers note there were some limitations to the study, including
the use of genetic tools and viral vectors to increase the levels of
neurturin, which isn't directly applicable from a therapeutic standpoint.

This study was financed by the Swedish Research Council, the Novo
Nordisk Foundation, the Swedish Diabetes Foundation, the Strategic
Research Program (SRP) in Diabetes, and The Lars Hiertas Memorial
Foundation. Sandra Kleiner, Michael Stec and Naveen Khan are employees
and shareholders of Regeneron Pharmaceuticals, Inc. Jorge Lira Ruas
is a consultant for Bayer AG. There are no other reported conflicts
of interest.

========================================================================== Story Source: Materials provided by Karolinska_Institutet. Note: Content
may be edited for style and length.


========================================================================== Journal Reference:
1. Jorge C. Correia, Yildiz Kelahmetoglu, Paulo R. Jannig, Christoph
Schweingruber, Dasa Svaikovskaya, Liu Zhengye, Igor Cervenka,
Naveen Khan, Michael Stec, Mariana Oliveira, Jik Nijssen,
Vicente Marti'nez- Redondo, Serge Ducommun, Michele Azzolini,
Johanna T. Lanner, Sandra Kleiner, Eva Hedlund, Jorge Lira
Ruas. Muscle-secreted neurturin couples myofiber oxidative
metabolism and slow motor neuron identity. Cell Metabolism, 2021
DOI: 10.1016/j.cmet.2021.09.003 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2021/09/210929112811.htm

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