Researchers have discovered a regulatory process that helps control the maturation of brain cells. This regulation seems to be defective in multiple sclerosis, disrupting the ability of cells to repair damage. The findings, which have been reported in Cell, provides new insights into the mechanisms of cellular maturation, and could help researchers develop new treatments for some neurological disorders.
In multiple sclerosis, the protective insulation surrounding neurons, called myelin, is damaged. Cells called oligodendrocytes could repair this damage, and this study has revealed a the "molecular brake that controls when oligodendrocytes mature,” explained senior study author Paul Tesar, a professor at Case Western Reserve University's School of Medicine, among other appointments.
Multiple sclerosis gets progressively worse, and there are no therapeutics that can restore lost myelin. But this study has identified “a clear path to unlocking the brain's own repair program,” added Tesar. "We believe these new insights will help deliver on the promise of regenerative therapies that [multiple sclerosis] patients so urgently need."
Oligodendrocytes are a type of glial cell; about half of the cells in the human nervous system are glial cells, but we still don’t know a lot about all of their functions. In this study, scientists aimed to learn more about how oligodendrocytes sheath neurons in myelin. Oligodendriocytes must be mature to perform this function.
The researchers determined that a protein called SOX6 is crucial to the maturation of oligodendrocytes; it can function as a brake that halts maturation with a process called gene melting. Gene melting refers to extensive remodeling of the three-dimensional structure of DNA and the proteins that organize it, which are known as chromatin; chromatin remodeling can have a significant influence on the physical availability of genes, and thus, gene expression. In the case of SOX6, the halting of oligodendrocyte maturation through gene melting prevents the premature formation of myelin, and works like a protective timer. But in multiple sclerosis, this mechanism appears to go awry.
In multiple sclerosis patients, there were abnormally high levels of cells in an immature state, stuck by SOX6.
When the researchers reduced the number of SOX6 cells in mouse models, the oligodendrocytes matured and started to remyelinate local neurons.
"Our findings suggest that oligodendrocytes in [multiple sclerosis] are not permanently broken, but may simply be stalled," said co-first study author Jesse Zhan, a medical student at Case Western. "More importantly, we show that it is possible to release the brakes on these cells to resume their vital functions in the brain."
Sources: Case Western Reserve University, Cell