王小川，博士生導師，教授，入選教育部新世紀優秀人才支持計劃，是中國藥理學會抗衰老及老年癡呆專業委員會副主任委員、湖北省微循環學會副理事長、武漢病理生理學會副理事長、神經系統重大疾病教育部重點實驗室辦公室主任、神經精神藥物藥理國家自然科學基金創新研究群體成員。長期堅持緻力于神經退行性疾病的基礎研究，在老年性癡呆症病因、發病機制、早期診斷、動物模型建立和防治策略等方面開展了系列研究，相關成果在國際上有影響力的刊物以通訊作者和共同作者在Mol Psychiatry， Alzheimer & Dementia，PNAS, Acta Neuropathol等雜志發表80多篇經國際同行評審文章。主持國家自然科學基金資助課題8項，作為主要成員獲教育部高等學校科學研究優秀成果獎自然科學獎一等獎兩次。主、參編17本次中英文病理生理學教材。多家國際期刊審稿人。

研究方向一：老年性癡呆症發病機制與防治策略。

老年癡呆症（亦稱阿爾茨海默病，Alzheimer’s disease, AD）是最常見的神經退行性疾病，随着社會人口的老齡化，AD患病人數急劇上升。目前我國AD患者達1000萬人，每年新增30萬。AD不僅嚴重危害人類健康，降低患者生活質量，而且給家庭和社會帶來了沉重的負擔。然而，迄今為止，AD的診斷策略模糊、發病機制亦未完全闡明，尚未篩選出十分理想的防治藥物。本人長期緻力于AD基礎研究，目前主要研究興趣領域：

1. 蛋白質翻譯後異常修飾參與 AD神經原纖維退變形成的機制研究；

2. 圍繞Tau磷酸化酯酶與激酶上遊關鍵分子探讨Tau異常過度磷酸化促進Tau病變及認知功能障礙；

3. 研究細胞周期相關子網絡關鍵基因介導AD病理過程；

4. AD模型構建；

5. 針對AD發病關鍵分子開展藥物篩選。

研究方向二：腦老化發病機制研究。

老化是一個由多因素協同引起的生命漸趨弱化的過程，會引發機體各種功能的衰退，進而誘發一系列包括癌症、糖尿病、心血管以及神經變性方面的疾病，甚至可導緻失能。目前，中國正在逐步邁入老齡化社會，60歲及以上的老人占總人口比例為15.5%，65歲及以上老人占比10.1%，到2035年中國老年人口将達到4億人，失能、半失能的具有神經退行性變化的老人數量将會急劇增加，将給社會和家庭帶來極大的負擔，因此對如何延緩衰老以及阻止衰老導緻的神經退行性變化的研究已成為當務之急。目前主要研究興趣領域：

1. P53蘇木化異常修飾參與腦老化機制研究；

2. 腦老化中蘇木化異常修飾參與AD神經原纖維退變形成機制。

近年作為負責人主持的課題：

1. 國家自然科學基金項目（海外及港澳學者合作研究基金延續資助項目）：CDT2介導Aβ毒性參與阿爾茨海默症的分子機制研究（31929002）， 2020.1-2023.12

2. 國家自然科學基金項目：CK2磷 酸化SET介導老年癡呆症Tau病理變化的機理研究（31771114）， 2018.1-2021.12

3. 華中科技大學學術前沿青年團隊項目：老年性癡呆症神經原纖維退變形成及其防治策略研究，2016.12-2021.12

4. 國家自然科學基金項目：蘇木(SUMO)化參與AD特征性病理變化機制的研究（81571255）， 2016.1-2019.12

5. 國家自然科學基金項目（海外及港澳學者合作研究基金）：CDT2介導CDK1活性在AD發病中的作用機理研究（31528010）， 2016.1-2017.12

6. 湖北省科技支撐計劃：一種基于發病學非轉基因老年癡呆症動物模型的建立(2015BCE094) ， 2015.10-2017.9

7. 國家自然科學基金項目：14-3-3蛋白在阿爾茨海默病SET核運輸中的作用及其機理研究（81271405）， 2013.1-2016.12

8. 國家自然科學基金項目 SET核運輸障礙及其在阿爾茨海默病中的作用和機理　（31071226）， 2011.1-2013.12

9. 國家自然科學基金項目 SET核轉運及其對PP2A活性影響　（30871259）， 2009.1-2009.12

10.教育部新世紀優秀人才支持計劃 NCET-07-0332阿爾茨海默病Tau蛋白微管重複結構域空間構象預測及針對分子靶的藥物篩選， 2008.1-2010.12

11.國家自然科學基金項目fMRI BOLD信号與AD樣tau異常的關系及其對AD早期預報的基礎研究 (30400103)，2005.1-2007.12

近年發表的主要論著：（通訊作者*）

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, Wang 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 I₂^PP2A/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