Scientists identify possible way to block muscle fatigue in long COVID, other diseases

Infections and neurodegenerative diseases cause inflammation in the brain. But for unknown reasons, patients with brain inflammation often develop muscle problems that seem unrelated to the central nervous system. Now, researchers at Washington University School of Medicine in St. Louis have uncovered how brain inflammation releases specific proteins that travel from the brain to muscles and cause loss of muscle function.

The study also identified a way to inhibit this process in fruit flies and mice, which Inflammatory disordersThese include bacterial infections, Alzheimer’s, and long COVID.

This study Published July 12th Journal Science Immunology.

“We’re interested in understanding the very severe muscle fatigue that’s associated with some common diseases,” said Aaron Johnson, PhD, senior author of the paper and associate professor of developmental biology.

“Our research suggests that when we get sick, messenger proteins from the brain travel through the bloodstream and reduce energy levels in skeletal muscles. This isn’t just because you’re feeling unwell and don’t have the motivation to move. These processes Energy levels in Skeletal muscleYour ability to move and function normally is reduced.”

To explore the impact of brain inflammation on muscle function, the researchers modeled three different types of the disease: Bacterial infectionSARS-CoV-2 virus infection and Alzheimer’s disease.

When the brain is exposed to inflammatory proteins characteristic of these diseases, Reactive oxygen species When reactive oxygen species accumulate Brain Cells It produces an immune-related molecule called interleukin-6 (IL-6), which circulates throughout the body via the bloodstream.

The researchers found that mouse IL-6 and its corresponding protein Fruit flies—Decreased energy production in muscle mitochondria, the energy factories of cells.

“Flies and mice with COVID-related proteins in their brains had impaired motor function — the flies couldn’t run as well as they should and the mice couldn’t run as well as the control mice,” Johnson said.

“We saw a similar effect on muscle function when the brain was exposed to bacteria-associated proteins and the Alzheimer’s protein amyloid-beta, and we also saw evidence that this effect can be chronic: even if the infection is quickly cleared, the decline in muscle performance in our experiments persisted for several days.”

Johnson, along with his collaborators at the University of Florida and lead author Shuo Yang, PhD, who worked on the study as a postdoctoral researcher in Johnson’s lab, argue that the same process is likely involved in humans.

Meningitis, a bacterial brain infection, is known to increase IL-6 levels and may be associated with muscle problems in some patients, for example: inflammatory SARS-CoV-2 proteins have been found in the brain in autopsies of COVID-19 patients, and many long COVID patients complain of extreme fatigue and muscle weakness, even long after they have cleared up from the initial infection.

Alzheimer’s patients not only exhibit muscle weakness but also elevated levels of IL-6 in their blood.

The study identifies potential targets for the prevention and treatment of muscle weakness. Brain inflammationThe researchers found that IL-6 activates a pathway in muscle called the JAK-STAT pathway, which is responsible for reducing mitochondrial energy production.

Several therapeutic drugs already approved by the Food and Drug Administration for other diseases can block this pathway: JAK inhibitors and several monoclonal antibodies against IL-6 have been approved for the treatment of various types of arthritis and for managing other inflammatory diseases.

“It’s unclear why the brain produces protein signals that are so detrimental to muscle function across so many different disease categories,” Johnson said.

“If we want to speculate as to why this process has persisted in us throughout human evolution, despite the damage it causes, it could be that it is the brain’s way of reallocating resources to itself when fighting disease. Further research is needed to better understand this process and its effects on the whole body.”

“In the meantime, we hope that our study will encourage further clinical research into this pathway and lead to whether existing therapies that block different parts of this pathway could help many patients who suffer from this type of debilitating muscle wasting,” he said.