王小川，博士生导师，教授，入选教育部新世纪优秀人才支持计划，是中国药理学会抗衰老及老年痴呆专业委员会副主任委员、湖北省微循环学会副理事长、武汉病理生理学会副理事长、神经系统重大疾病教育部重点实验室办公室主任、神经精神药物药理国家自然科学基金创新研究群体成员。长期坚持致力于神经退行性疾病的基础研究，在老年性痴呆症病因、发病机制、早期诊断、动物模型建立和防治策略等方面开展了系列研究，相关成果在国际上有影响力的刊物以通讯作者和共同作者在Mol Psychiatry， Alzheimer & Dementia，PNAS, Acta Neuropathol等杂志发表80多篇经国际同行评审文章。主持国家自然科学基金资助课题8项，作为主要成员获教育部高等学校科学研究优秀成果奖自然科学奖一等奖两次。主、参编17本次中英文病理生理学教材。多家国际期刊审稿人。

 

研究方向一：老年性痴呆症发病机制与防治策略。

老年痴呆症（亦称阿尔茨海默病，Alzheimer’s disease, AD）是最常见的神经退行性疾病，随着社会人口的老龄化，AD患病人数急剧上升。目前我国AD患者达1000万人，每年新增30万。AD不仅严重危害人类健康，降低患者生活质量，而且给家庭和社会带来了沉重的负担。然而，迄今为止，AD的诊断策略模糊、发病机制亦未完全阐明，尚未筛选出十分理想的防治药物。本人长期致力于AD基础研究，目前主要研究兴趣领域：

1. 蛋白质翻译后异常修饰参与 AD神经原纤维退变形成的机制研究；

2. 围绕Tau磷酸化酯酶与激酶上游关键分子探讨Tau异常过度磷酸化促进Tau病变及认知功能障碍；

3. 研究细胞周期相关子网络关键基因介导AD病理过程；

4. AD模型构建；

5. 针对AD发病关键分子开展药物筛选。

 

研究方向二：脑老化发病机制研究。

老化是一个由多因素协同引起的生命渐趋弱化的过程，会引发机体各种功能的衰退，进而诱发一系列包括癌症、糖尿病、心血管以及神经变性方面的疾病，甚至可导致失能。目前，中国正在逐步迈入老龄化社会，60岁及以上的老人占总人口比例为15.5%，65岁及以上老人占比10.1%，到2035年中国老年人口将达到4亿人，失能、半失能的具有神经退行性变化的老人数量将会急剧增加，将给社会和家庭带来极大的负担，因此对如何延缓衰老以及阻止衰老导致的神经退行性变化的研究已成为当务之急。目前主要研究兴趣领域：

1. P53苏木化异常修饰参与脑老化机制研究；

2. 脑老化中苏木化异常修饰参与AD神经原纤维退变形成机制。

近年作为负责人主持的课题：

1. 国家自然科学基金项目（海外及港澳学者合作研究基金延续资助项目）：CDT2介导Aβ毒性参与阿尔茨海默症的分子机制研究（31929002）， 2020.1-2023.12

2. 国家自然科学基金项目：CK2磷 酸化SET介导老年痴呆症Tau病理变化的机理研究（31771114）， 2018.1-2021.12

3. 华中科技大学学术前沿青年团队项目：老年性痴呆症神经原纤维退变形成及其防治策略研究，2016.12-2021.12

4. 国家自然科学基金项目：苏木(SUMO)化参与AD特征性病理变化机制的研究（81571255）， 2016.1-2019.12

5. 国家自然科学基金项目（海外及港澳学者合作研究基金）：CDT2介导CDK1活性在AD发病中的作用机理研究（31528010）， 2016.1-2017.12

6. 湖北省科技支撑计划：一种基于发病学非转基因老年痴呆症动物模型的建立(2015BCE094) ， 2015.10-2017.9

7. 国家自然科学基金项目：14-3-3蛋白在阿尔茨海默病SET核运输中的作用及其机理研究（81271405）， 2013.1-2016.12

8. 国家自然科学基金项目 SET核运输障碍及其在阿尔茨海默病中的作用和机理　（31071226）， 2011.1-2013.12

9. 国家自然科学基金项目 SET核转运及其对PP2A活性影响　（30871259）， 2009.1-2009.12

10.教育部新世纪优秀人才支持计划 NCET-07-0332阿尔茨海默病Tau蛋白微管重复结构域空间构象预测及针对分子靶的药物筛选， 2008.1-2010.12

11.国家自然科学基金项目fMRI BOLD信号与AD样tau异常的关系及其对AD早期预报的基础研究 (30400103)，2005.1-2007.12

近年发表的主要论著：（通讯作者*）

1. Xia Y, Wang ZH, Liu P, Edgington-Mitchell L, Liu X, Wang XC*, Ye K. TrkB receptor cleavage by delta-secretase abolishes its phosphorylation of APP, aggravating Alzheimer's disease pathologies. Mol Psychiatry. 2020 Aug 11. doi: 10.1038/s41380-020-00863-8. Online ahead of print.

2. Xu J, Guo C, Liu Y, Wu G, Ke D, Wang Q, Mao J, Wang JZ, Liu R, Wang XC*. Nedd4l downregulation of NRG1 in the mPFC induces depression-like behaviour in CSDS mice. Transl Psychiatry. 2020 Jul 23;10(1):249. doi: 10.1038/s41398-020-00935-x.

3. Guo C, Liu Y, Fang M, Li Y, Li W, Mahaman YAR, Zeng K, Xia Y, Ke D, Liu R, Wang JZ, Shen H, Shu X, Wang XC*. ω-3PUFAs improves cognitive impairments through Ser133 phosphorylation of CREB up-regulating BDNF/TrkB signal in schizophrenia. Neurotherapeutics, 2020. May 4. doi: 10.1007/s13311-020-00859-w. Online ahead of print.

4. Wan L, Zhang Q, Luo H, Xu Z, Huang S, Yang F, Liu Y, Mahaman YAR, Ke D, Wang Q, Liu R, Wang JZ, Shu X, Wang XC*. Codonopsis pilosula Polysaccharide attenuates Aβ toxicity and cognitive defects in APP/PS1 mice. Aging, 2020 Jul 11;12(13):13422-13436. doi: 10.18632/aging.103445.

5. Huang F, Wang M, Liu R, Wang JZ, Schadt E, Haroutunian V, Katsel P, Zhang B, Wang XC*. CDT2 Controlled Cell Cycle Reentry Regulates the Pathogenesis of Alzheimer’s Disease. Alzheimers & Dementia. 2019 Feb;15(2):217-231. doi: 10.1016/j.jalz.2018.08.013. Epub 2018 Oct 12.

6. Mahaman YAR, Huang F, Henok KA, Maibouge TMS, Ghose B, Wang XC*. Involvement of calpain in the neuropathogenesis of Alzheimer’s Disease. Medicinal Research Reviews. 2019 Mar;39(2):608-630. doi: 10.1002/med.21534.

7. Qin M, Li H, Bao J, Xia Y, Ke D, Wang Q, Liu R, Wang JZ, Zhang B, Shu X, Wang XC*. SET SUMOylation promotes its cytoplasmic retention and induces tau pathology and cognitiveimpairments. Acta Neuropathol Commun. 2019 Feb 15;7(1):21. doi: 10.1186/s40478-019-0663-0.

8. Wei Z, Mahaman YAR, Zhu F, Wu M, Xia Y, Zeng K, Yang Y, Liu R, Wang JZ, Shu X, Wang XC*. GSK-3β and ERK1/2 incongruously act in tau hyperphosphorylation in SPS-induced PTSD rats. Aging (Albany NY). 2019 Sep 23;11(18):7978-7995. doi: 10.18632/aging.102303. Epub 2019 Sep 23.

9. Li X, Run X, Wei Z, Zeng K, Liang Z, Huang F, Ke D, Wang Q, Wang JZ, Liu R, Zhang B, Wang XC*. Intranasal insulin prevents anesthesia-induced cognitive impairments in aged mice. Curr Alzheimer Res. 2019;16(1):8-18. doi: 10.2174/1567205015666181031145045.

10. Zhang Q, Xia Y, Wang Y, Luo H, Huang S, Wang Y, Shentu Y, Mahaman YAR, Huang F, Wu M, Ke D, Wangg Q, Liu R, Wang JZ, Zhang B, Wang XC*. Codonopsis pilosula Polysaccharide attenuates tau hyperphosphorylation and cognitive impairments in hTau infected mice. Front Mol Neurosci. 2018 Nov 27;11:437. doi: 10.3389/fnmol.2018.00437. eCollection 2018.

11. Maibouge TMS, Mahaman YAR, Zhu F, Huang F, Wang Y, Xu Z, Ke D, Wang Q, Liu R, Wang JZ, Zhang B, Wang XC* Methanolic extract of Tamarix Gallica attenuates hyperhomocysteinemia induced AD-like pathology and cognitive impairments in rats. Aging (Albany NY). 2018 Nov 12;10(11):3229-3248. doi: 10.18632/aging.101627.

12. Wu M, Yu G, Yan T, Ke D, Wang Q, Liu R, Wang JZ, Zhang B, Chen D, Wang XC*. Phosphorylation of SET mediates apoptosis via P53 hyperactivation and NM23-H1 nuclear import. Neurobiol Aging. 2018 Sep;69:38-47. doi: 10.1016/j.neurobiolaging.2018.04.022.

13. Bao J, Qin M, Mahaman YAR，Zhang B, Huang F, Zeng K, Xia Y, Ke D, Wang Q, Liu R, Wang JZ, Ye K, Wang XC*. BACE1 SUMOylation increases its stability and escalates the protease activity in Alzheimer’s disease. Proc Natl Acad Sci U S A. 2018 Apr 10;115(15):3954-3959. doi: 10.1073/pnas.1800498115.

14. Zhang Q, Xia Y, Wang Y, Shentu Y, Zeng K, Mahaman YAR, Huang F, Wu M, Ke D, Wang Q, Zhang B, Liu R, Wang JZ, Ye K, Wang XC*. CK2 Phosphorylating I2PP2A/SET Mediates Tau Pathology and Cognitive Impairment. Front Mol Neurosci. 2018 Apr 30;11:146. doi: 10.3389/fnmol.2018.00146. eCollection 2018.

15. Mahaman YAR, Huang F, Wu M, Wang Y, Wei Z, Bao J, Salissou MTM, Ke D, Wang Q, Liu R, Wang JZ, Zhang B, Chen D, Wang XC*. Moringa Oleifera Alleviates Homocysteine-Induced Alzheimer's Disease-Like Pathology and Cognitive Impairments. J Alzheimers Dis. 2018;63(3):1141-1159. doi: 10.3233/JAD-180091.

16. Zeng K, Li M, Hu J, Mahaman YAR, Bao J, Huang F, Xia Y, Liu X, Wang Q, Wang JZ, Yang Y, Liu R, Wang XC*. Ginkgo biloba extract EGb761 attenuates Hyperhomocysteinemia-induced AD like tau hyperphosphorylation and cognitive impairment in rats. Curr Alzheimer Res. 2018;15(1):89-99.

17. Liu X, Zeng K, Li M, Wang Q, Liu R, Zhang B, Wang JZ, Shu X, Wang XC*. Expression of P301L-hTau in mouse MEC induces hippocampus-dependent memory deficit. Sci Rep. 2017 Jun 20;7(1):3914. doi: 10.1038/s41598-017-04305-4.

18. Fang MS, Li X, Qian H, Zeng K, Ye M, Zhou YJ, Li H, Wang XC*, Li Y. ω-3PUFAs prevent MK-801-induced cognitive impairment in schizophrenic rats via the CREB/BDNF/TrkB pathway. J Huazhong Univ Sci Technolog Med Sci. 2017 Aug;37(4):491-495

19. Wang XC, Blanchard J, Tung YC, Grundke-Iqbal I, Iqbal K*. Inhibition of Protein Phosphatase-2A (PP2A) by I1PP2A Leads to Hyperphosphorylation of Tau, Neurodegeneration and Cognitive Impairment in Rats. J Alzheimers Dis. 2015 Jan 1;45(2):423-435. doi: 10.3233/JAD-142403.

20. Wang XC, Blanchard J, Grundke-Iqbal I, Wegiel J, Deng HX, Siddique T, Iqbal K. Alzheimer disease and amyotrophic lateral sclerosis: an etiopathogenic connection. Acta Neuropathol. 2014 Feb;127(2):243-256.

21. Luo HB, Xia YY, Shu XJ, Liu ZC, Feng Y, Liu XH, Yu G, Yin G, Xiong YS, Zeng K, Jiang J, Ye K, Wang XC*, Wang JZ*. SUMOylation at K340 inhibits tau degradation through deregulating its phosphorylation and ubiquitination. Proc Natl Acad Sci U S A. 2014 Nov 18;111(46):16586-16591.

22. Xia Y, Liu R, Chen R, Tian Q, Zeng K, Hu J, Liu X, Wang Q, Wang P, Wang XC*, Wang JZ*. Novel Multipotent AChEI-CCB Attenuates Hyperhomocysteinemia-Induced Memory Deficits and Neuropathologies in Rats. J Alzheimers Dis. 2014; 42(3):1029-1039.

23. Liu XH, Wang ZH, Xia YY, Yu G, Zeng K, Luo HB, Hu JC, Gong CX, Wang JZ, Zhou XW, Wang XC*. Losartan-induced hypotension leads to tau hyperphosphorylation and memory deficit. J Alzheimers Dis. 2014;40(2):419-27

24. Yu G, Yan TH, Feng Y, Liu XH, Xia YY, Luo HB, Wang JZ, Wang XC*. Ser9 phosphorylation causes cytoplasmic detention of I2PP2A/SET in Alzheimer disease. Neurobiology of Aging. 2013 Jul;34(7):1748-1758

25. Feng Y, Xia Y, Yu G, Shu X, Ge H, Zeng K, Wang J, Wang XC*. Cleavage of GSK-3β by calpain counteracts the inhibitory effect of Ser9 phosphorylation on GSK-3β activity induced by H2O2. J Neurochem. 2013 Jul; 126(2):234-42. doi: 10.1111/jnc.12285.

26. Feng Y, Wang XC*. Antioxidant therapies for Alzheimer's disease. Oxid Med Cell Longev. 2012;2012:472932. doi: 10.1155/2012/472932.

27. Yu G, Li Y, Tian Q, Liu R, Wang Q, Wang JZ, Wang XC*. Berberine Attenuates Calyculin A-Induced Cytotoxicity and Tau Hyperphosphorylation in HEK293 Cells. J Alzheimers Dis. 2011; 24(3):525-535

28. Wang XC, Blanchard J, Kohlbrenner E, Clement N, Linden RM, Radu A, Grundke-Iqbal I, Iqbal K. The carboxy-terminal fragment of inhibitor-2 of protein phosphatase-2A induces Alzheimer disease pathology and cognitive impairment. FASEB J. 2010; 24(11):4420-4432.

29. Wang XC*, Zhang YC, Chatterjie N, Grundke-Iqbal,I,.Iqbal K, Wang JZ, Effect of Melatonin and Melatonylvalpromide on beta-amyloid and Neurofilaments in N2a Cells. Neurochem Res. 2008; 33(6):1138-1144.

30. Wang XC, Du XX, Tian Q, Wang JZ. Correlation between Choline Signal Intensity and Acetylcholine Level in Different Brain Regions of Rat. Neurochem Res. 2008; 33(5):814-819.

31. Wang Q, Tian Q, Liu R, Liu ZZ, Hu MQ, Ke D, Zhang SH, Wang XC*. Pre-treatment of Melatonin against Oleic Acid-Induced Acute Lung Injury in Rats. Chinese Journal of Pathophysiology, 2007, 23(4): 767-771

32. Wang XC, Zhang J, Yu X, Han L, Zhou ZT, Zhang Y, Wang JZ. Prevention of isoproterenol-induced tau hyperphosphorylation by melatonin in the rat. Acta Physiologica Sinica. 2005; 57(1): 7-12

33. Wang XC, Hu ZH, Tang XW, Wu YG, Wang JZ. Correlation of Alzheimer-like tau abnormal hyperphosphorylation and fMRI BOLD signal intensity. Current Alzheimer Research. 2004; 1(2): 143-145