New Reseach on AKG and Brain Health

Important study on alpha ketoglutarate and brain function just published in Nature, one of the most prestigious scientific journals.

In summary, the study suggests that the gene DOR plays a critical role in helping produce myelin. When this gene isn't working properly, oligodendrocytes struggle to repair myelin. However, alpha-ketoglutarate (AKG) can help fix these issues, leading to better myelin repair and potentially improved brain function during aging or disease.

The study focuses on the process of remyelination, which is when damaged myelin—the protective covering around nerve fibers—gets repaired. Myelin damage occurs in diseases like multiple sclerosis and also as people age. Oligodendrocytes are the cells responsible for producing myelin, but as they mature, they lose some ability to do this efficiently, which affects remyelination.

In conditions like multiple sclerosis and aging, oligodendrocytes become less able to make myelin, but scientists don’t fully understand why.

The researchers found a gene called DOR (also known as TP53INP2), which is important for myelin production. This gene is found in mature oligodendrocytes, but it is less active in people with multiple sclerosis and older individuals.

When they removed the Dor gene in mice, the animals showed problems in producing and repairing myelin. DOR and another factor called SOX10 work together to control the activity of genes needed for myelin production. One important gene they regulate is Prr18, which helps oligodendrocytes function properly.

DOR is also important for producing a molecule called α-ketoglutarate, which is crucial for energy production and fat (lipid) synthesis in the cells. These processes are necessary for myelin formation. In mice that lacked DOR, giving them α-ketoglutarate (a supplement) fixed their oligodendrocyte maturation problems and improved their ability to repair myelin after it had been damaged. This treatment also improved cognitive function in older mice, suggesting it could have benefits beyond just myelin repair.

The researchers propose that activating α-ketoglutarate metabolism in mature oligodendrocytes could help boost myelin production in diseases like multiple sclerosis and as part of the aging process.