Hypermyelination
of the SN of Gtf2i-KO mice. Credit: Nature Communications (2025). DOI: 10.1038/s41467-025-63500-4
Researchers from Tel Aviv University have discovered a new biological
mechanism that enhances the production of myelin—a substance essential for
proper brain function and nerve communication.
"Our findings may serve as the basis for developing innovative
treatments for severe neurological disorders involving myelin damage, including
multiple sclerosis, Alzheimer's disease, and certain neurodevelopmental
syndromes," the researchers note.
The study was conducted in the laboratory of Prof. Boaz Barak of the Sagol
School of Neuroscience and the School of Psychological Sciences at Tel Aviv
University and led by Dr. Gilad Levy. The lab collaborated with researchers
from the Hebrew University of Jerusalem, the Weizmann Institute of Science, Tel
Aviv University, and Germany's Max Planck Institute.
The findings are published in Nature Communications.
Releasing the brain's 'biological brakes'
Prof. Barak explains, "Damage to myelin is associated with a variety
of neurodegenerative diseases such as Alzheimer's disease and multiple
sclerosis (an autoimmune disease in which the body itself attacks the myelin),
as well as neurodevelopmental syndromes like Williams syndrome and autism spectrum disorders.
"In this study we focused on the cells that produce myelin in both the
central and peripheral nervous systems. Specifically in these cells, we
investigated the role of a protein called Tfii-i, known for its ability to
increase or decrease the expression of many genes crucial for cell function.
"While Tfii-i has long been linked to abnormal brain development and
neurodevelopmental syndromes, its role in myelin production had not been
studied until now."
Prof. Barak's team discovered that the Tfii-i acts as a "biological brake" that inhibits myelin production in the relevant cells. Based on this finding, the researchers hypothesized that reducing Tfii-i activity in myelinating cells might increase myelin output.
Testing the hypothesis
To test this, the team used advanced genetic engineering in model mice:
Tfii-i expression was selectively eliminated only in myelin-producing cells,
while remaining unchanged in all other cells.
These genetically modified mice were compared to normal mice on a wide
variety of measures, including levels of myelin proteins, structure and
thickness of the myelin sheath surrounding axons, speed of nerve signal
conduction, and even motor and behavioral performance.
Dr. Gilad Levy explains, "We found that in the absence of Tfii-i, the
myelin-producing cells generated higher amounts of myelin proteins. This
resulted in abnormally thick myelin sheaths, which enhanced the conduction
speed of electrical signals along the neural axons. These improvements resulted
in a significant enhancement of the mice's motor abilities, including better
coordination and mobility, along with other behavioral benefits."
Prof. Barak concludes, "In this study we demonstrated for the first
time that it is possible to 'release the brakes' on myelin production in the
brain and peripheral nervous system by regulating the expression of Tfii-i.
"This study is among the few to identify a mechanism for increasing
myelin levels in the brain. Its results may enable the development of future
therapies that suppress Tfii-i activity in myelin-producing cells, to restore
myelin in a wide variety of degenerative and developmental diseases in
which myelin is
impaired—including Alzheimer's disease, multiple sclerosis, Williams syndrome,
and autism spectrum disorders.
"We believe this fundamentally new approach holds great therapeutic potential."
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