Browsing by Author "Qiu, Mengsheng"

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    ADAMTS4 Enhances Oligodendrocyte Differentiation and Remyelination by Cleaving NG2 Proteoglycan and Attenuating PDGFRα Signaling
    (Society for Neuroscience, 2023) Jiang, Chunxia; Qiu, Wanwan; Yang, Yingying; Huang, Hao; Dai, Zhong-min; Yang, Aifen; Tang, Tao; Zhao, Xiaofeng; Qiu, Mengsheng; Anatomy, Cell Biology and Physiology, School of Medicine
    Although NG2 is known to be selectively expressed in oligodendrocyte precursor cells (OPCs) for many years, its expressional regulation and functional involvement in oligodendrocyte differentiation have remained elusive. Here, we report that the surface-bound NG2 proteoglycan can physically bind to PDGF-AA and enhances PDGF receptor alpha (PDGFRα) activation of downstream signaling. During differentiation stage, NG2 protein is cleaved by A disintegrin and metalloproteinase with thrombospondin motifs type 4 (Adamts4), which is highly upregulated in differentiating OPCs but gradually downregulated in mature myelinating oligodendrocytes. Genetic ablation of Adamts4 gene impedes NG2 proteolysis, leading to elevated PDGFRα signaling but impaired oligodendrocyte differentiation and axonal myelination in both sexes of mice. Moreover, Adamts4 deficiency also lessens myelin repair in adult brain tissue following Lysophosphatidylcholine-induced demyelination. Thus, Adamts4 could be a potential therapeutic target for enhancing oligodendrocyte differentiation and axonal remyelination in demyelinating diseases. SIGNIFICANCE STATEMENT: NG2 is selectively expressed in OPCs and downregulated during differentiation stage. To date, the molecular mechanism underlying the progressive removal of NG2 surface proteoglycan in differentiating OPCs has been unknown. In this study, we demonstrate that ADAMTS4 released by differentiating OPCs cleaves surface NG2 proteoglycan, attenuates PDGFRα signaling, and accelerates oligodendrocyte differentiation. In addition, our study also suggests ADAMTS4 as a potential therapeutic target for promoting myelin recovery in demyelinating diseases.
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    Hedgehog Signaling in CNS Remyelination
    (MDPI, 2022-07-21) Fang, Minxi; Tang, Tao; Qiu, Mengsheng; Xu, Xiaofeng; Anatomy, Cell Biology and Physiology, School of Medicine
    Remyelination is a fundamental repair process in the central nervous system (CNS) that is triggered by demyelinating events. In demyelinating diseases, oligodendrocytes (OLs) are targeted, leading to myelin loss, axonal damage, and severe functional impairment. While spontaneous remyelination often fails in the progression of demyelinating diseases, increased understanding of the mechanisms and identification of targets that regulate myelin regeneration becomes crucial. To date, several signaling pathways have been implicated in the remyelination process, including the Hedgehog (Hh) signaling pathway. This review summarizes the current data concerning the complicated roles of the Hh signaling pathway in the context of remyelination. We will highlight the open issues that have to be clarified prior to bringing molecules targeting the Hh signaling to demyelinating therapy.
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    Immunological Markers for Central Nervous System Glia
    (Springer, 2023) Huang, Hao; He, Wanjun; Tang, Tao; Qiu, Mengsheng; Anatomy, Cell Biology and Physiology, School of Medicine
    Glial cells in the central nervous system (CNS) are composed of oligodendrocytes, astrocytes and microglia. They contribute more than half of the total cells of the CNS, and are essential for neural development and functioning. Studies on the fate specification, differentiation, and functional diversification of glial cells mainly rely on the proper use of cell- or stage-specific molecular markers. However, as cellular markers often exhibit different specificity and sensitivity, careful consideration must be given prior to their application to avoid possible confusion. Here, we provide an updated overview of a list of well-established immunological markers for the labeling of central glia, and discuss the cell-type specificity and stage dependency of their expression.