Recently, a team led by Professor Massimiliano Mazzone (VIB-KU Leuven Cancer Biology Center) collaborated with Dr. Emanuele Berardi and Dr. Min Shang to reveal a new metabolic dialogue between inflammatory cells and muscle stem cells. Researchers have shown that enhancing this metabolic crosstalk with GLUD1 inhibitors can promote the release of glutamine and improve muscle regeneration and body function in experimental models of muscle degeneration such as trauma, ischemia, and aging. In addition to its transformational potential, this work also provides important advances in multiple research fields including muscle biology, immune metabolism and stem cell biology.
The role of glutamine
Skeletal muscle helps our body move, but it is also a large amount of amino acid reserves stored in the form of protein, which affects the energy and protein metabolism of the entire human body. The role of the amino acid glutamine is considered essential for muscle metabolism due to its abundance. However, its exact role after trauma or during chronic muscle degenerative diseases is largely ignored.
Professor Massimiliano Mazzone’s research team observed that during damage or aging, the normal level of glutamine in muscles is reduced due to dead muscle tissue. The researchers determined the metabolic dialogue between the inflammatory cells that arrived after injury and the resident muscle stem cells. This cell crosstalk can re-establish the original level of glutamine in the muscle and promote muscle fiber regeneration in the process.
Regenerate muscle
Researchers have used the latest in vitro and in vivo techniques and methods to show that muscle damage, ischemia, and aging-related muscle wasting are characteristics of reduced glutamine. One of the reasons for this is the loss of glutamine production due to the damage of the muscle itself.
Dr. Berardi explained: “Using genetic tools and the pharmacology of the enzyme GLUD1 that inhibits glutamine metabolism, we can prevent the decline of glutamine after injury. This leads to excessive glutamine production by inflammatory cells called macrophages. And then it reaches muscle damage. The newly produced glutamine can be used by muscle stem cells to quickly regenerate damaged muscle tissue. We have found the same thing in acute and chronic degenerative diseases (such as aging), thereby enabling muscle function Recovery is faster."
prevent degeneration
This study reveals that glutamine acts as a sensor molecule whose level in muscle tissue controls the regeneration process and shows that GLUD1 is a therapeutic target that can be used after acute injury or chronic degenerative diseases (such as aging) Muscle regeneration provides opportunities.
Professor Mazzone emphasized the potential of his discovery: "This provides hope for the treatment of degenerative muscle diseases (including trauma, ischemia and aging). As the average age of the global population continues to increase, with the development of health, the latter is particularly beneficial Healthcare poses a major challenge. With the joint efforts of VIB Discovery Sciences and the Center for Drug Design and Discovery, we are currently developing and testing more selective GLUD1 inhibitors to treat chronic muscular dystrophy, including muscular dystrophy. ."