ADAMTS4 Enhances Oligodendrocyte Differentiation and Remyelination by Cleaving NG2 Proteoglycan and AttenuatingPDGFRα Signaling

• DOI: 10.1523/jneurosci.2146-22.2023
• Publication Date: 2023-05-15T17:50:57Z
• Authors: Chunxia Jiang; Wanwan Qiu; Yingying Yang; Hao Huang; Zhong-min Dai; Aifen Yang; Tao Tang; Xiaofeng Zhao; Mengsheng Qiu
• Keywords: Remyelination

Although NG2 is known to be selectively expressed in oligodendrocyte precursor cells (OPCs) for many years, its expressional regulation and functional involvement differentiation have remained elusive. Here, we report that the surface-bound proteoglycan can physically bind PDGF-AA enhances PDGF receptor alpha ( PDGFR α) activation of downstream signaling. During stage, protein cleaved by A disintegrin metalloproteinase with thrombospondin motifs type 4 Adamts4 ), which highly upregulated differentiating OPCs but gradually downregulated mature myelinating oligodendrocytes. Genetic ablation gene impedes proteolysis, leading elevated PDGFRα signaling impaired axonal myelination both sexes mice. Moreover, deficiency also lessens myelin repair adult brain tissue following Lysophosphatidylcholine-induced demyelination. Thus, could a potential therapeutic target enhancing remyelination demyelinating diseases. SIGNIFICANCE STATEMENT during stage. To date, molecular mechanism underlying progressive removal surface has been unknown. In this study, demonstrate ADAMTS4 released cleaves proteoglycan, attenuates signaling, accelerates differentiation. addition, our study suggests as promoting recovery