Cellular Pathway Essential for Myelin-Forming Cells
It may be a target for demyelinating diseases such as multiple sclerosis
TUESDAY, May 19 (HealthDay News) -- Activation of a cellular signaling pathway is essential for the differentiation of myelin-forming oligodendrocytes, which could represent a target in demyelinating diseases such as multiple sclerosis, according to a study in the May 13 issue of the Journal of Neuroscience.
William A. Tyler, from the University of Medicine and Dentistry of New Jersey in Newark, and colleagues investigated the intracellular signaling pathways leading to differentiation of oligodendrocyte progenitor cells into mature oligodendrocytes in mice.
The researchers found that the mammalian target of rapamycin (mTOR) was activated at the transition from late progenitor to immature oligodendrocyte, as determined by the expression of stage-specific antigens and myelin proteins. In the developing brain, modification of mTOR by phosphorylation was associated with myelination in the subcortical white matter. Inhibition of the formation of mTOR protein complexes significantly reduced the expression of myelin, while inhibition of mTOR strongly inhibited oligodendrocyte differentiation and reduced the numbers of myelin segments.
"These data support the hypothesis that mTOR regulates commitment to oligodendrocyte differentiation before myelination," Tyler and colleagues conclude. "Signaling via mTOR represents an intriguing target for therapeutic intervention to promote remyelination in disorders such as multiple sclerosis."