A study led by Dr. Hyun Kyoung Lee, associate professor at Baylor College of Medicine and investigator at the Jan and Dan Duncan Neurological Research Institute at Texas Children's Hospital, has discovered a new biological mechanism to regenerate and repair myelin, a protective sheath that insulates neuronal fibers and plays a vital role in ensuring rapid and accurate neurotransmission.
Reviewed by Megan Craig, M.Sc.Aug 24 2023 The Duncan NRI team found novel roles for the Dishevelled associated activator of morphogenesis 2 protein and CK2α kinase in regulating myelin repair and regeneration. The study was published in the Proceedings of the National Academy of Science.
A few years back, Dr. Lee and others found that a glial protein, Daam2 inhibits the differentiation of oligodendrocytes during development as well as myelin regeneration and repair. However, until now precise mechanisms underlying this process have remained a mystery. Since Daam2 is a known positive modulator of canonical Wnt signaling, they examined whether these DEGs were due to perturbations in Wnt signaling. They undertook a thorough developmental stage-specific analysis which revealed dynamic changes in the machinery and function of Wnt/β-catenin signaling in early versus late stages of OL development, and established that this signaling pathway is affected by Daam2 phosphorylation.
Related StoriesTo identify the kinase responsible for Daam2 phosphorylation, they conducted a motif analysis which found CK2, a Wnt/β-catenin signaling Ser/Thr kinase that was also one of the candidates in their biochemical and genetic screen. They further confirmed that its catalytic subunit, CK2α, interacted with Daam2 in lab-cultured OLs and also phosphorylated it. Moreover, both Daam2 and CK2α were sequentially upregulated in a manner that was concomitant with the progression of OL lineage.
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A new pathway to regenerate myelin discoveredA study led by Dr. Hyun Kyoung Lee, associate professor at Baylor College of Medicine and investigator at the Jan and Dan Duncan Neurological Research Institute at Texas Children's Hospital, has discovered a new biological mechanism to regenerate and repair myelin, a protective sheath that insulates neuronal fibers and plays a vital role in ensuring rapid and accurate neurotransmission.
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