厦门大学南强特聘教授，博士生导师 国家杰出青年科学基金获得者 研究方向：阿尔茨海默病的神经免疫机制和新药物靶点 所在系部：神经科学研究所 办公电话：0592-2182261 邮    箱：wangx@xmu.edu.cn 课题组网页：http://wangxlab.xmu.edu.cn/

研究领域

课题组聚焦阿尔茨海默病的外周–中枢神经免疫互作及其药物靶点，面向神经科学与免疫学交叉前沿，系统解析该疾病外周与中枢相互作用的分子机制，并积极探索其在转化医学中的应用。旨在为阿尔茨海默病的精准诊断和创新治疗策略提供坚实的理论基础和实验依据。近年来，团队成员在Cell、Nature Neuroscience、Nature Medicine、Journal of Clinical Investigation、Science Advances、National Science Review、Molecular Psychiatry、PLoS Biology 等国际学术期刊发表系列研究成果。基于临床样本和多种疾病动物模型，我们以独特的学术视角和系统化研究方法，深入揭示外周免疫与中枢神经系统相互作用在阿尔茨海默病发生发展中的关键机制。当前的主要研究方向包括：

1. 揭示外周-中枢免疫调控异常介导阿尔茨海默病发病的分子与细胞生物学机制；

2. 鉴定外周-中枢免疫互作通路中的新型药物靶点，并针对阿尔茨海默病开展高效药物筛选与靶向药物效应机制研究。

学习经历

2009~2013 美国Sanford-Burnham医学研究所Biomedical Sciences专业  博士；

2005~2008 上海交通大学药学院药理学专业  硕士研究生；

2001~2005 重庆医科大学药学院药学专业    理学学士。

工作经历

2015~至今 yl23411永利官网登录  教授；

2014~2015 美国Sanford-Burnham医学研究所  博士后；

2013~2014 美国加州大学圣地亚哥分校（UCSD）神经科学系、霍华德•休斯医学研究所（HHMI）  博士后；

2013~2013 美国Sanford-Burnham医学研究所  博士后；

2008~2009 美国Sanford-Burnham医学研究所  访问学者。

代表性成果

1.Gao Y, Hong Y, Huang L, Zheng S, Zhang H, Wang S, Yao Y, Zhao Y, Zhu L, Xu Q, Chai X, Zeng Y, Zeng Y, Zheng L, Zhou Y, Luo H, Zhang X, Zhang H, Zhou Y, Fu G, Sun H, Huang TY, Zheng Q, Xu H, Wang X*. β2-microglobulin functions as an endogenous NMDAR antagonist to impair synaptic function. Cell. 2023;186(5):1026-1038.

2.Zhao Y, Zheng Q, Hong Y, Gao Y, Hu J, Lang M, Zhang H, Zhou Y, Luo H, Zhang X, Sun H, Yan XX, Huang TY, Wang YJ, Xu H, Liu C, Wang X*. β2-microglobulin coaggregates with Aβ and contributes to amyloid pathology and cognitive deficits in Alzheimer’s disease model mice. Nat Neurosci. 2023;26(7):1170-1184.（封面论文）

3.Zhang H^#, Zheng Q^#, Guo T^#, Zhang S^#, Zheng S, Wang R, Deng Q, Yang G, Zhang S, Tang L, Qi Q, Zhu L, Zhang X-F, Luo H, Zhang X, Sun H, Gao Y, Zhang H, Zhou Y, Han A, Zhang C-S, Xu H, Wang X*. Metabolic reprogramming in astrocytes results in neuronal dysfunction in intellectual disability. Mol Psychiatry. 2022. DOI: 10.1038/s41380-022-01521-x.

4.Zheng Q^#, Song B^#, Li G^#, Cai F^#, Wu M, Zhao Y, Jiang L, Guo T, Shen M, Hou H, Zhou Y, Zhao Y, Di A, Zhang L, Zeng F, Zhang X-F, Luo H, Zhang X, Zhang H, Zeng Z, Huang T, Dong C, Qing H, Zhang Y, Zhang Q, Wang X, Wu Y, Xu H*, Song W*, and Wang X*. USP25 inhibition ameliorates Alzheimer’s pathology through regulating APP processing and Aβ generation. J Clin Invest. 2022;132(5): e15217

5.Zhang H^#, Hong Y^#, Yang W, Wang R, Yao T, Wang J, Liu K, Yuan H, Xu C, Zhou Y, Li G, Zhang L, Luo H, Zhang X, Du D, Sun H, Zheng Q, Zhang Y-W, Zhao Y, Zhou Y, Xu H, Wang X*. SNX14 deficiency-induced defective axonal mitochondrial transport in Purkinje cells underlies cerebellar ataxia and can be reversed by valproate. Natl Sci Rev. 2021;8(7): nwab024.

6.Zheng Q^#, Li G^#, Wang S, Zhou Y, Liu K, Gao Y, Zhou Y, Zheng L, Zhu L, Deng Q, Wu M, Di A, Zhang L, Zhao Y, Zhang H, Sun H, Dong C, Xu H, Wang X*. Trisomy 21-induced dysregulation of microglial homeostasis in Alzheimer’s brains is mediated by USP25. Sci Adv. 2021;7(1): eabe1340.

7.Zeng F^#, Ma X^#, Zhu L^#, Xu Q, Zeng Y, Gao Y, Li G, Guo T, Zhang H, Tang X, Wang Z, Ye Z, Zheng L, Zhang H, Zheng Q, Li K, Lu J, Qi X, Luo H, Zhang X, Wang Z, Zhou Y, Yao Y, Ke R, Zhou Y, Liu Y, Sun H, Huang T, Shao Z, Xu H, and Wang X*. The deubiquitinase USP6 affects memory and synaptic plasticity through modulating NMDA receptor stability. PLoS Biol. 2019;17(12): e3000525.

8.Wang X, Zhao Y, Zhang X, Badie H, Zhou Y, Mu Y, Loo LS, Cai L, Thompson RC, Yang B, Chen Y, Johnson PF, Wu C, Bu G, Mobley WC, Zhang D, Gage FH, Ranscht B, Zhang YW, Lipton SA, Hong W, Xu H*. Loss of sorting nexin 27 contributes to excitatory synaptic dysfunction via modulation of glutamate receptor recycling in Down's syndrome. Nat Med. 2013;19(4):473-80. （封面论文）

承担的重要研究项目

1.国家自然科学基金杰出青年科学基金项目，82325018，2024-01至2028-12，主持；

2.国家自然科学基金区域联合基金重点项目，U21A20358，2022-01至2025-12，主持；

3.科技部重点研发计划课题，2021YFA1101401，2021-12至2026-06，主持；

4.科技部科技创新2030—“脑科学与类脑研究”重大项目，2021ZD0202402，2021-12至2026-11，骨干；

5.福建省自然科学基金重点项目，2021J02004，2021-11至2024-11，主持；

6.广东省基础与应用基础研究基金区域联合基金重点项目，2021B1515120081，2021-10至2024-09，主持；

7.国家自然科学基金优秀青年科学基金项目，81822014，2019-1至2021-12，主持；

8.国家自然科学基金面上项目，31871077，2019-1至2022-12，主持；

9.福建省自然科学基金杰出青年基金项目，2017J06021，2017-4至2020-4，主持；

10.国家自然科学基金面上项目，81571176，2016-1至2019-12，主持。

获奖及荣誉

1.国家杰出青年科学基金获得者，2023年；

2.第十七届福建省青年科技奖，2023年；

3.厦门市科技进步一等奖，2018年；

4.厦门市首批杰出青年人才，2018年；

5.基金委优秀青年科学基金获得者，2018年；

6.福建省引进高层次创新人才计划专家，2017年；

7.福建省杰出青年基金获得者，2017年；

8.闽江学者特聘教授，2016年；

9.国家高层次青年人才，2016年；

10.美国阿尔茨海默病协会青年学者奖（Young Scholar Award of Alzheimer's Association），2010年。

所有论文列表

1.Zhang S, Gao Y, Zhao Y, Huang TY, Zheng Q*, Wang X*. Peripheral and central neuroimmune mechanisms in Alzheimer's disease pathogenesis. Mol Neurodegener. 2025;20(1):22. DOI: 10.1186/s13024-025-00812-5.   PMID: 39985073

2.Zheng Q*, Wang X*. Alzheimer's disease: insights into pathology, molecular mechanisms, and therapy. Protein Cell. 2025;16(2):83-120. DOI: 10.1093/procel/pwae026.   PMID: 38733347

3.Qiao M^#, Huang Q^#, Wang X*, Han J*. ZBTB21 suppresses CRE-mediated transcription to impair synaptic function in Down syndrome. Sci Adv. 2024;10(27):eadm7373. DOI: 10.1126/sciadv.adm7373.   PMID: 38959316

4.Zhang H*, Wang X*. The Role of Protein Quantity Control in Polyglutamine Spinocerebellar Ataxias. Cerebellum. 2024;23(6):2575-2592. DOI: 10.1007/s12311-024-01722-w.   PMID: 39052145

5.Zhong L*, Sheng X, Wang W, Li Y, Zhuo R, Wang K, Zhang L, Hu DD, Hong Y, Chen L, Rao H, Li T, Chen M, Lin Z, Zhang YW, Wang X, Yan XX, Chen X, Bu G, Chen XF*. TREM2 receptor protects against complement-mediated synaptic loss by binding to complement C1q during neurodegeneration. Immunity. 2023;56(8):1794-1808.e8.   PMID: 37442133

6.Zhao Y, Zheng Q, Hong Y, Gao Y, Hu J, Lang M, Zhang H, Zhou Y, Luo H, Zhang X, Sun H, Yan XX, Huang TY, Wang YJ, Xu H, Liu C, Wang X*. β2-microglobulin coaggregates with Aβ and contributes to amyloid pathology and cognitive deficits in Alzheimer’s disease model mice. Nat Neurosci. 2023.   PMID: 37264159

7.Gao Y, Hong Y, Huang L, Zheng S, Zhang H, Wang S, Yao Y, Zhao Y, Zhu L, Xu Q, Chai X, Zeng Y, Zeng Y, Zheng L, Zhou Y, Luo H, Zhang X, Zhang H, Zhou Y, Fu G, Sun H, Huang TY, Zheng Q, Xu H, Wang X*. β2-microglobulin functions as an endogenous NMDAR antagonist to impair synaptic function. Cell. 2023.   PMID: 36868208

8.Li X, Hu B, Guan X, Wang Z, Zhou Y, Sun H, Zhang X, Li Y, Huang X, Zhao Y, Wang X, Xu H, Zhang YW, Wang Z*, Zheng H*. Minocycline protects against microgliopathy in a Csf1r haplo-insufficient mouse model of adult-onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP). J Neuroinflammation. 2023;20(1):134. DOI: 10.1186/s12974-023-02774-1.   PMID: 37259140

9.Zhang H^#, Zheng Q^#, Guo T^#, Zhang S^#, Zheng S, Wang R, Deng Q, Yang G, Zhang S, Tang L, Qi Q, Zhu L, Zhang X-F, Luo H, Zhang X, Sun H, Gao Y, Zhang H, Zhou Y, Han A, Zhang C-S, Xu H, Wang X*. Metabolic reprogramming in astrocytes results in neuronal dysfunction in intellectual disability. Mol Psychiatry. 2022.   PMID: 35338313

10.Zheng Q^#, Song B^#, Li G^#, Cai F^#, Wu M, Zhao Y, Jiang L, Guo T, Shen M, Hou H, Zhou Y, Zhao Y, Di A, Zhang L, Zeng F, Zhang X-F, Luo H, Zhang X, Zhang H, Zeng Z, Huang T, Dong C, Qing H, Zhang Y, Zhang Q, Wang X, Wu Y, Xu H*, Song W*, and Wang X*. USP25 inhibition ameliorates Alzheimer’s pathology through regulating APP processing and Aβ generation. J Clin Invest. 2022;132(5): e15217.  PMID: 35229730

11.Tang XY, Xu L, Wang J, Hong Y, Wang Y, Zhu Q, Wang D, Zhang XY, Liu CY, Fang KH, Han X, Wang S, Wang X, Xu M, Bhattacharyya A, Guo X*, Lin M*, Liu Y*. DSCAM/PAK1 pathway suppression reverses neurogenesis deficits in iPSC-derived cerebral organoids from patients with Down syndrome. J Clin Invest. 2021;131(12): e135763.  PMID: 33945512

12.Zhang H^#, Hong Y^#, Yang W, Wang R, Yao T, Wang J, Liu K, Yuan H, Xu C, Zhou Y, Li G, Zhang L, Luo H, Zhang X, Du D, Sun H, Zheng Q, Zhang Y-W, Zhao Y, Zhou Y, Xu H, Wang X*. SNX14 deficiency-induced defective axonal mitochondrial transport in Purkinje cells underlies cerebellar ataxia and can be reversed by valproate. Natl Sci Rev. 2021;8(7): nwab024.  PMID: 34691693

13.Zheng Q^#, Li G^#, Wang S, Zhou Y, Liu K, Gao Y, Zhou Y, Zheng L, Zhu L, Deng Q, Wu M, Di A, Zhang L, Zhao Y, Zhang H, Sun H, Dong C, Xu H, Wang X*. Trisomy 21-induced dysregulation of microglial homeostasis in Alzheimer’s brains is mediated by USP25. Sci Adv. 2021;7(1): eabe1340.  PMID: 33523861

14.Huo Y^#, Gao Y^#, Zheng Q, Zhao D, Guo T, Zhang S, Zeng Y, Cheng Y, Gu H, Zhang L, Zhu B, Luo H, Zhang X, Zhou Y, Zhang YW, Sun H, Xu H, Wang X*. Overexpression of Human SNX27 Enhances Learning and Memory Through Modulating Synaptic Plasticity in Mice. Front Cell Dev Biol. 2020;8:595357.  PMID: 33330482

15.Lin C^#, Jiang M^#, Liu L^#, Chen X, Zhao Y, Chen L, Hong Y, Wang X, Hong C, Yao X, Ke R*. Imaging of individual transcripts by amplification-based single-molecule fluorescence in situ hybridization. N Biotechnol. 2021;61:116-123.  PMID: 33301924

16.Zhao D, Zhou Y, Huo Y, Meng J, Xiao X, Han L, Zhang X, Luo H, Can D, Sun H, Huang TY, Wang X, Zhang J, Liu FR, Xu H, Zhang YW*. RPS23RG1 modulates tau phosphorylation and axon outgrowth through regulating p35 proteasomal degradation. Cell Death Differ. 2021;28(1):337-348.  PMID: 32908202

17.Rong Z, Cheng B, Zhong L, Ye X, Li X, Jia L, Li Y, Shue F, Wang N, Cheng Y, Huang X, Liu CC, Fryer JD, Wang X, Zhang YW, Zheng H*. Activation of FAK/Rac1/Cdc42-GTPase signaling ameliorates impaired microglial migration response to Aβ42 in triggering receptor expressed on myeloid cells 2 loss-of-function murine models. FASEB J. 2020;34(8):10984-10997.  PMID: 32613609

18.Lin C, Jiang M, Duan S, Qiu J, Hong Y, Wang X, Chen X, Ke R*. Visualization of individual microRNA molecules in fixed cells and tissues using target-primed padlock probe assay. Biochem Biophys Res Commun. 2020;526(3):607-611.  PMID: 32247612

19.Zeng F^#, Ma X^#, Zhu L^#, Xu Q, Zeng Y, Gao Y, Li G, Guo T, Zhang H, Tang X, Wang Z, Ye Z, Zheng L, Zhang H, Zheng Q, Li K, Lu J, Qi X, Luo H, Zhang X, Wang Z, Zhou Y, Yao Y, Ke R, Zhou Y, Liu Y, Sun H, Huang T, Shao Z, Xu H, and Wang X*. The deubiquitinase USP6 affects memory and synaptic plasticity through modulating NMDA receptor stability. PLoS Biol. 2019;17(12): e3000525.  PMID: 31841517

20.Zhang H^#, Zhu L^#, Wang F^#, Wang R, Hong Y, Chen Y, Zhu B, Gao Y, Luo H, Zhang X, Sun H, Zhou Y*, Yao Y*, Wang X*. Novel KCNJ10 Compound Heterozygous Mutations Causing EAST/SeSAME-Like Syndrome Compromise Potassium Channel Function. Front Genet. 2019;10:912.  PMID: 31781151

21.Lin KM^#, Su G^#, Wang F, Zhang X, Wang Y, Ren J, Wang X*, Yao Y*, Zhou Y*. A de novo SCN8A heterozygous mutation in a child with epileptic encephalopathy: a case report. BMC Pediatr. 2019;19(1):400.  PMID: 31672125

22.Zeng Y, Wang N, Guo T, Zheng Q, Wang S, Wu S, Li X, Wu J, Chen Z, Xu H, Wang X*, Lin B*. Snx27 Deletion Promotes Recovery From Spinal Cord Injury by Neuroprotection and Reduces Macrophage/Microglia Proliferation. Front Neurol. 2018;9:1059.  PMID: 30619032

23.Zhao D, Meng J, Zhao Y, Huo Y, Liu Y, Zheng N, Zhang M, Gao Y, Chen Z, Sun H, Wang X, Jing C, Zhang T, Zhang X, Luo H, Wang X, Zhang J, Liu FR, Li Y, Bu G, Wen L, Huang TY, Xu H, Zhang YW. RPS23RG1 Is Required for Synaptic Integrity and Rescues Alzheimer's Disease-Associated Cognitive Deficits. Biol Psychiatry. 2018. pii: S0006-3223(18)31782-7.  PMID: 30292394

24.Zhang H, Huang T, Hong Y, Yang W, Zhang X, Luo H, Xu H, Wang X*. The Retromer Complex and Sorting Nexins in Neurodegenerative Diseases. Front Aging Neurosci. 2018;10:79.  PMID: 29632483

25.Zhao Y, Li X, Huang T, Jiang LL, Tan Z, Zhang M, Cheng IH, Wang X, Bu G, Zhang YW, Wang Q, Xu H. Intracellular trafficking of TREM2 is regulated by presenilin 1. Exp Mol Med. 2017;49(12):e405.  PMID: 29611543

26.Zheng H, Jia L, Liu CC, Rong Z, Zhong L, Yang L, Chen XF, Fryer JD, Wang X, Zhang YW, Xu H, Bu G*. TREM2 Promotes Microglial Survival by Activating Wnt/β-catenin Pathway. J Neurosci. 2017;37(7):1772-1784.   PMID: 28077724

27.Zheng Q, Huang T, Zhang L, Zhou Y, Luo H, Xu H, Wang X*. Dysregulation of Ubiquitin-Proteasome System in Neurodegenerative Diseases. Front Aging Neurosci. 2016;8:303.   PMID: 28018215

28.Wang X*, Zhou Y, Wang J, Tseng IC, Huang T, Zhao Y, Zheng Q, Gao Y, Luo H, Zhang X, Bu G, Hong W, Xu H*. SNX27 Deletion Causes Hydrocephalus by Impairing Ependymal Cell Differentiation and Ciliogenesis. J Neurosci. 2016;36(50):12586-12597.  PMID: 27974614

29.Huang TY, Zhao Y, Li X, Wang X, Tseng IC, Thompson R, Tu S, Willnow TE, Zhang YW, Xu H*. SNX27 and SORLA Interact to Reduce Amyloidogenic Subcellular Distribution and Processing of Amyloid Precursor Protein. J Neurosci. 2016;36(30):7996-8011.   PMID: 27466343

30.Zhang X, Hu J, Zhong L, Wang N, Yang L, Liu CC, Li H, Wang X, Zhou Y, Zhang Y, Xu H, Bu G*, Zhuang J*. Quercetin stabilizes apolipoprotein E and reduces brain Aβ levels in amyloid model mice. Neuropharmacology. 2016;108:179-192.   PMID: 27114256

31.Zhao Y, Tseng IC, Heyser CJ, Rockenstein E, Mante M, Adame A, Zheng Q, Huang T, Wang X, Arslan PE, Chakrabarty P, Wu C, Bu G, Mobley WC, Zhang YW, St George-Hyslop P, Masliah E, Fraser P, Xu H*. Appoptosin-Mediated Caspase Cleavage of Tau Contributes to Progressive Supranuclear Palsy Pathogenesis. Neuron. 2015;87(5):963-75.   PMID: 26335643

32.Aquizu N, Cantagrel V, Zaki M, Al-Gazali L, Wang X, et al. Biallelic mutations in SNX14 lead to a syndromic form of cerebellar atrophy and lysosome-autophagosome dysfunction. Nat Genet. 2015;47(5):528-34.   PMID: 25848753

33.Wang X, Huang T, Zhao Y, Thompson RC, Bu G, Zhang YW, Hong W, Xu H*. Sorting nexin 27 regulates Aβ production through modulating γ-secretase activity. Cell Rep. 2014;9(3):1023-33.   PMID: 25437557

34.Wang X, Huang T, Bu G, Xu H*. Dysregulation of protein trafficking in neurodegeneration. Mol Neurodegener. 2014;9(1):31.   PMID: 25152012

35.Wang X, Zhao Y, Zhang X, Badie H, Zhou Y, Mu Y, Loo LS, Cai L, Thompson RC, Yang B, Chen Y, Johnson PF, Wu C, Bu G, Mobley WC, Zhang D, Gage FH, Ranscht B, Zhang YW, Lipton SA, Hong W, Xu H*. Loss of sorting nexin 27 contributes to excitatory synaptic dysfunction via modulation of glutamate receptor recycling in Down's syndrome. Nat Med. 2013;19(4):473-80.  PMID: 23524343

36.Zhao Y, Wang Y, Yang J, Wang X, Zhao Y, Zhang X, Zhang YW*. Sorting nexin 12 interacts with BACE1 and regulates BACE1-mediated APP processing. Mol Neurodegener. 2012; 7(30).   PMID: 22709416

37.Liu Y, Zhang YW, Wang X, Zhang H, You X, Liao FF, Xu H*. Intracellular trafficking of Presenilin 1 is regulated by β-amyloid precursor protein and phospholipase D1. J Biol Chem. 2009; 284(18):12145-52.   PMID: 19276086

38.Nie H, Li Z, Lukas RJ, Shen Y, Song L, Wang X, Yin M*. Construction of SH-EP1-alpha4beta2-hAPP695 cell line and effects of nicotinic agonists on beta-amyloid in the cells. Cell Mol Neurobiol. 2008;28(1):103-12.   PMID: 17912626