MicroRNA-200s attenuate demyelination caused by Angiostrongylus cantonensis in a mouse model by targeting phosphatase and tensin homologOA
Demyelinating diseases of the central nervous system are common,yet few effective strategies for myelin repair and remyelination are available.An increasing number of studies highlight the role of microRNAs(miRNAs)as key regulators of demyelination.miRNA mimics and inhibitors,which are currently in preclinical development,have shown promise as novel therapeutic agents.However,the mechanisms by which they protect myelin are not fully understood.Using a mouse model of acute central nervous system demyelination induced by infection with Angiostrongylus cantonensis,we investigated alterations in miRNA expression in the mouse brain.Our findings revealed a significant early-stage increase in the levels of miR-200,particularly miR-200a and miR-200c.Subsequent analysis demonstrated that combined miR-200a and miR-200c overexpression improved neurobehavioral outcomes and attenuated demyelination in Angiostrongylus cantonensis-infected mice.Further lipid metabolomic profiling indicated that miR-200a and miR-200c synergistically inhibited the production of phosphatase and tensin homolog(PTEN)and activated the phosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin signaling pathway,as confirmed by double luciferase reporter assay and western blotting.Additionally,in vitro experiments showed that miR-200a and miR-200c protected oligodendrocyte precursor cells from lipopolysaccharide-induced damage and enhanced their survival.Our study indicates the critical role of miR-200a and miR-200c in protecting against central nervous system demyelination by targeting PTEN and modulating key survival pathways.Furthermore,our findings suggest that miR-200a and miR-200c are promising diagnostic biomarkers of and therapeutic targets for treating demyelination-related disorders.
Huihui Xiong;Zhixuan Ma;Ge Li;Zhen Niu;Liang Yang;Xiaojie Wu;Liming Wang;Fukang Xie;Chi Teng Vong;Xi Sun;Zhongdao Wu;Ying Feng
School of Medicine,South China University of Technology,Guangzhou,Guangdong Province,China Zhongshan School of Medicine,Sun Yat-sen University,Guangzhou,Guangdong Province,ChinaSchool of Medicine,South China University of Technology,Guangzhou,Guangdong Province,ChinaGuangdong Provincial Key Laboratory of Pathogenesis,Targeted Prevention and Treatment of Heart Disease,Guangdong Provincial People’s Hospital(Guangdong Academy of Medical Sciences),Southern Medical University,Guangzhou,Guangdong Province,ChinaSchool of Medicine,South China University of Technology,Guangzhou,Guangdong Province,ChinaSchool of Medicine,South China University of Technology,Guangzhou,Guangdong Province,ChinaSchool of Medicine,South China University of Technology,Guangzhou,Guangdong Province,ChinaGuangdong Provincial Key Laboratory of Pathogenesis,Targeted Prevention and Treatment of Heart Disease,Guangdong Provincial People’s Hospital(Guangdong Academy of Medical Sciences),Southern Medical University,Guangzhou,Guangdong Province,ChinaZhongshan School of Medicine,Sun Yat-sen University,Guangzhou,Guangdong Province,ChinaState Key Laboratory of Quality Research in Chinese Medicine,Institute of Chinese Medical Sciences,University of Macao,Macao Special Administrative Region,China Macao Center for Research and Development in Chinese Medicine,University of Macao,Macao Special Administrative Region,ChinaZhongshan School of Medicine,Sun Yat-sen University,Guangzhou,Guangdong Province,ChinaZhongshan School of Medicine,Sun Yat-sen University,Guangzhou,Guangdong Province,ChinaSchool of Medicine,South China University of Technology,Guangzhou,Guangdong Province,China
医药卫生
Angiostrongylus cantonensiscentral nervous systemdemyelinationendogenousmiR-200sphosphatase and tensin homolog
《Neural Regeneration Research》 2026 (6)
P.2599-2608,10
supported by the National Natural Science Foundation of China,Nos.82372277(to ZW),82272361(to XS),82271395(to GL)Guangdong Province Basic and Applied Basic Research Fund Project,No.2024A1515010615(to XS)Guangdong Province Natural Youth Promotion Project,No.2314070000241(to GL)Guangzhou Science and Technology Project,No.2025A04J4740(to GL).
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