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Wnt Signaling in Remyelination in Multiple Sclerosis: Friend or Foe?

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Abstract

Myelination is critical to normal functioning of the vertebrate nervous system. In demyelinating diseases such as multiple sclerosis, oligodendrocytes, the myelinating cells in the central nervous system, are targeted, resulting in myelin loss, axonal damage, and severe functional impairment. While spontaneous remyelination has been proven a failure in multiple sclerosis, understanding the molecular mechanism underlying oligodendrocyte biology, myelination, and remyelination becomes crucial. To date, a series of signaling pathways in regulating oligodendrocyte development and remyelination have been suggested and, among them, the Wnt/β-catenin/Tcf pathway has been considered a negative factor in the myelinating process. However, this notion has been challenged by recent studies, which showed a pro-myelinating effect of this pathway. This review summarizes the current contradictory concepts concerning the role of the Wnt pathway in the oligodendrocyte development and remyelination process, attempts to address the potential mechanism underlying this controversy, and recommends caution in targeting the Wnt pathway as a potential demyelinating therapy.

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Acknowledgments

This work was supported by the National Natural Science Foundations of China (81230027, 81070959) and Key Scientific and Technological Project of Shanghai (11411950300). We thank Katherine Regan for the editorial assistance.

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The authors have no conflict of interest.

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  1. Department of Neurology, Changhai Hospital, Second Military Medical University, Shanghai, 200433, China

    Chong Xie, Zezhi Li, Guang-Xian Zhang & Yangtai Guan

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Correspondence to Guang-Xian Zhang or Yangtai Guan.

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Xie, C., Li, Z., Zhang, GX. et al. Wnt Signaling in Remyelination in Multiple Sclerosis: Friend or Foe?. Mol Neurobiol 49, 1117–1125 (2014). https://doi.org/10.1007/s12035-013-8584-6

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