Scientists have uncovered the mechanism of neuron death in multiple sclerosis

Scientists at the University of California at San Francisco, the University of Cambridge and Cedars-Sinai Medical Center have found that multiple sclerosis destroys the neurons of the cerebral cortex through DNA damage, which causes inflammation. The results of two related studies were published in the journal Medical Xpress.

"Now we can point to a specific mechanism of death of vulnerable neurons — DNA damage — and begin the fight against multiple sclerosis on a fundamentally new front," said co—author Steve Fancy, professor at the UCSF Institute of Neurology.

Until now, multiple sclerosis has been studied primarily as a disease of the white matter of the brain, the myelin—coated pathways. The new data explain why MRI scans of patients show lesions not only of white matter, but also of gray matter — the part of the brain where the bodies of nerve cells responsible for thinking and cognitive functions are located. This is a special type of lesion, more difficult to distinguish in photographs, but characteristic of chronic and disabling forms of the disease.

The researchers focused on the neurons expressing the CUX2 gene. In the first study conducted on mice, scientists found that during the period of active brain growth, these cells protect their DNA with the help of the ATF4 stress gene. When it was turned off, the neurons accumulated extensive DNA damage, and the frontal lobe of the brain did not form. In the second study, the same pattern was reproduced in gray matter samples from people with multiple sclerosis: chronic inflammation triggered chemical reactions that damaged the DNA of CUX2 neurons, and protective systems sufficient to withstand developmental stresses could no longer cope with this load.

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"CUX2 neurons are a kind of canary in the mine for the brain affected by multiple sclerosis. If we can protect these cells, we may be able to contain the progression of the disease," said co—author David Rowanich, professor of pediatrics at the University of Cambridge.

The authors emphasized that the results indicate the need to look for new treatment approaches that directly protect gray matter neurons, in addition to existing therapies aimed at restoring myelin. Multiple sclerosis remains one of the most common neurological diseases: according to the World Health Organization, it affects about 3 million people worldwide.

On March 2, Medical Xpress pointed to new markers of multiple sclerosis in the cerebrospinal fluid. During the analysis, the researchers identified a set of proteins capable of improving the differentiation of MS from other inflammatory brain diseases, especially in the absence of classical markers. In addition, it was found that changes in the proteome of the cerebrospinal fluid can potentially predict the further course of the disease.

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