A biological pathway through which myelin, the protective coating on nerve fibers, can be repaired and regenerated has been discovered in a new study. The ramifications of this finding could be far-reaching for those with neurological diseases affecting myelin, many of which are currently untreatable.
If the axons that shoot out from the cell bodies of neurons are like electrical wires, you can think of the myelin sheath as the insulating plastic outer coating. In the brain, these sheathed nerve fibers make up most of the tissue known as white matter, but axons throughout the body are also coated in myelin.
The myelin sheath’s main functions are to protect the axon, to ensure electrical nerve impulses can travel quickly down it, and to maintain the strength of these impulses as they travel over what can be very long distances.
A number of diseases are associated with damage to or destruction of the myelin sheath. These are called demyelinating diseases, the most well-known of which is probably multiple sclerosis. Brain injuries can also cause damage to myelin. Finding a way to help the sheath to repair itself could open the door to game-changing treatments for these conditions.
In the brain, myelin is produced by a specialized subset of cells called oligodendrocytes. Scientists previously observed that a protein called Daam2 can stop oligodendrocytes from generating new myelin and inhibit myelin repair, but until now it was unclear exactly how this happened.
A team led by Dr Hyun Kyoung Lee, an associate professor at Baylor College of Medicine and principal investigator at Texas Children’s Hospital, performed biochemical studies and genetic analyses in mice expressing a form of Daam2 that had been altered by phosphorylation, changing its function.
“Intriguingly, we found Daam2 phosphorylation differentially impacts distinct stages of oligodendrocyte development – in early stages, it accelerates the conversion of precursor [oligodendrocytes] to glial cells but in later stages, it slows down their maturation and their ability to produce myelin,” Dr Lee said in a statement.
Enzymes that phosphorylate other proteins are known as kinases. Dr Lee and the team performed further analysis and discovered that the kinase responsible for phosphorylating Daam2 in this case was called CK2α.
Using a mouse model of a brain injury sometimes seen in neonates, where the baby has been deprived of oxygen during birth, the team found that CK2α-mediated Daam2 phosphorylation had a protective role. It was also found to help restore myelin in adult animals that had sustained an injury to the brain’s white matter.
These functions of CK2α and Daam2 have never been observed before in the lab. Restoring lost myelin has long been a goal of research, and further work building on these findings could lead to much-needed treatments for the millions of people affected by demyelinating disease.
Dr Lee concluded, “This study opens exciting therapeutic avenues we could develop in the future to repair and restore myelin, which has the potential to alleviate and treat several neurological [diseases] that are currently untreatable.”
The study is published in the Proceedings of the National Academy of Sciences.
