王建枝 华中科技大学同济医学院病理生理学教授。获国家杰出青年基金、教育部长江学者特聘教授、入选国家万人计划领军人才，被评为国家教学名师、全国师德标兵和全国三八红旗手。从事老年性痴呆（AD）研究近30年，在揭示tau蛋白异常导致AD神经退行性变性机制及其诊治策略方面取得系统性创新成果。发表SCI论文200余篇，其中包括第Nat Med，Mol Cell, Neuron, Nat Struct Mol Biol, Nat Commun, Prog Neurobiol, PNAS, J Neurosci等国际高影响力杂志，被SCI杂志正面6000余次；2014至2017年连续被Elsevier列入中国高被引学者榜单；相关研究成果以第一完成人获国家自然科学奖二等奖1项、省部级自然科学奖一等奖4项。在武汉领导建立的AD研究基地被“Current Biology”列为中国神经科学和神经疾病研究8大旗舰中心之一。目前兼任教育部神经疾病重点实验室主任、湖北省病理生理学会理事长、国际病理生理学会副会长等；主编国家规划教材《病理生理学》第六、七、八、九版，英文版、双语版和长学制教材第三版；担任JAD，Neurosci Bull等多个国际杂志的副主编以及J Neurochem等杂志的handling editor或编委等。
研究方向：老年性痴呆（即阿尔茨海默病，AD）发病机制和早期诊治策略
目前的研究课题：1. AD神经退变的本质以及骨架蛋白tau的作用和机制； 2. 不同情绪影响空间记忆的神经环路基础和作用机制；3. 2型糖尿病向AD转化的机制及其早期预测；4. AD高危因素的人群队列研究；5. AD有效干预药物研究。
代表性论文(选自>200篇)：
1. Wang ZH, Liu P, Liu X, Manfredsson FP, Sandoval IM, Yu SP, Wang JZ*, Ye K*. Delta-Secretase Phosphorylation by SRPK2 Enhances Its Enzymatic Activity, Provoking Pathogenesis in Alzheimer's Disease. Mol Cell. 2017 Sep 7;67(5):812-825.e5. doi: 10.1016/j.molcel.2017.07.018. Epub 2017 Aug 17.
2. Zhang Z, Kang SS, Liu X, Zhang Z, He l, Iuvone PM, Duong DM, Seyfried NT, Benskey MJ, Manfredsoon FP, Jin L, Sun YE, Wang JZ*, Ye K*. Asparagine endopeptidase cleaves synuclein and mediates its pathological activities in Parkinson disease. Nature Structural & Molecular Biology. 2017 Jul 3. doi: 10.1038/nsmb.3433. [Epub ahead of print].
3. Zhang Z, Obianyo O, Dall E, Du Y, Fu H, Liu X, Kang SS, Song M, Yu SP, Cabrele C, Schubert M, Li X, Wang JZ*, Brandstetter H*, Ye K*. Inhibition of delta-secretase improves cognitive functions in mouse models of Alzheimer's disease. Nat Commun. 2017 Mar 27;8:14740. doi: 10.1038/ncomms14740.
4. Li XG, Wang ZH, Tan L, Wang YL, Lu C, Chen R, Zhang SJ, Gao Y, Liu YC, Yin YL, Liu XH, Liu EJ, Yang Y, Hu Y, Xu ZP, Xu FQ, Wang J, Liu GP, Wang JZ. Correcting miR92a-vGAT-mediated GABAergic dysfunctions rescues human tau-induced anxiety in mice. Mol Ther. 2017 25(1):140-152.
5. Yang Y, Wang ZH, Jin S, Gao D, Liu N, Chen SH, Zhang S, Liu Q, Liu E, Wang X, Liang L, Wei P, Li X, Li Y, Yue C, Li HL, Wang YL, Wang Q, Ke D, Xie Q, Xu F, Wang L, Wang JZ. Opposite monosynaptic scaling of BLP–vCA1 inputs governs hopefulness– and helplessness–modulated spatial learning and memory. Nat Commun. 2016;7:11935. doi:10.1038/ncomms11935.
6. Yin Y, Gao D, Wang Y, Wang ZH, Wang X, Ye J, Wu D, Fang L, Pi G, Yang Y, Wang XC, Lu C, Ye K, Wang JZ. Tau accumulation induces synaptic impairment and memory deficit by calcineurin-mediated inactivation of nuclear CaMKIV/CREB signaling. Proc Natl Acad Sci U S A. 2016 Jun 28;113(26):E3773-81.
7. Xu ZP，Yang SL，Zhao S，Zheng CH，Li HH，Zhang Y，Huang RX，Li MZ，Gao Y，Zhang SJ，Zhan PY，Zhang LF，Deng L，Wei S，Liu YC，Ye JW，Ren HJ，Li N，Kong CX，Wang X，Fang L，Zhou QZ，Jiang HW，Li JR，Wang Q，Ke D，Liu GP，Wang JZ. Biomarkers for Early Diagnostic of Mild Cognitive Impairment in Type-2 Diabetes Patients: A Multicentre, Retrospective, Nested Case-Control Study. EBioMedicine. 2016,5:105-113.
8. Liu D, Wei N, Man HY, Lu Y, Zhu LQ, Wang JZ. The MT2 receptor stimulates axonogenesis and enhances synaptic transmission by activating Akt signaling. Cell Death Differ. 2015 Apr;22(4):583-96.
9. 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.
10. Zhang Z, Song M, Liu X, Kang SS, Kwon IS, Duong DM, Seyfried NT, Hu WT, Liu Z, Wang JZ, Cheng L, Sun YE, Yu SP, Levey AI, Ye K. Cleavage of tau by asparagineendopeptidase mediates the neurofibrillary pathology in Alzheimer's disease. Nat Med. 2014 Nov;20(11):1254-62.
11. Liu GP, Wei W, Zhou X, Shi HR, Liu XH, Chai GS, Yao XQ, Zhang JY, Peng CX, Hu J, Li XC, Wang Q, Wang JZ. Silencing PP2A inhibitor by lenti-shRNA interference ameliorates neuropathologies and memory deficits in tg2576 mice. Mol Ther. 2013 Dec;21(12):2247-57.
12. Yang Y, Shu X, Liu D, Shang Y, Wu Y, Pei L, Xu X, Tian Q, Zhang J, Qian K, Wang YX, Petralia RS, Tu W, Zhu LQ, Wang JZ, Lu Y. EPAC null mutation impairs learning and social interactions via aberrant regulation of miR-124 and Zif268translation. Neuron. 2012 Feb 23;73(4):774-88.
13. Sun XY, Wei YP, Xiong Y, Wang XC, Xie AJ, Wang XL, Yang Y, Wang Q, Lu YM, LiuR, Wang JZ. Synaptic released zinc promotes tau hyperphosphorylation by inhibition of protein phosphatase 2A (PP2A). J Biol Chem. 2012 Mar 30;287(14):11174-82. Epub 2012 Feb 10.
14. Liu X, Bates R, Yin DM, Shen C, Wang F, Su N, Kirov SA, Luo Y, Wang JZ, Xiong WC, Mei L. Specific regulation of NRG1 isoform expression by neuronal activity. J Neurosci. 2011 Jun 8;31(23):8491-501.
15. Zhu LQ, Zheng HY, Peng CX, Liu D, Li HL, Wang Q and Wang JZ. Protein Phosphatase 2A Facilitates Axonogenesis by Dephosphorylating CRMP2. J Neurosci. 2010, 30:3839-3848.
16. Zhu LQ, Liu D, Hu J, Cheng J, Wang SH, Wang Q, Wang F, Chen JG, and Wang JZ. GSK-3b inhibits presynaptic vesicle exocytosis by phosphorylating P/Q-type calcium channel and interrupting SNARE complex formation. J Neurosci. 2010, 30:3824-3833.
17. Wang JZ, Liu F. Microtubule-associated protein tau in development, degeneration and protection of neurons. Prog Neurobiol. 2008, 85(2):148-175. An invited review.
18. Li HL, Wang HH, Liu SJ, Deng YQ, Zhang YJ, Tian Q, Wang XC, Chen XQ, Yang Y, Zhang JY, Wang Q, Xu H, Liao FF, Wang JZ. Phosphorylation of tau antagonizes apoptosis by stabilizing beta-catenin, a mechanism involved in Alzheimer's neurodegeneration. Proc Natl Acad Sci U S A. 2007, 104(9):3591-3596.
19. Zhu LQ, Wang SH, Yin YY, Liu D, Zheng HY, Shi HR, Tian Q, Wang XC, Wang Q, Chen JG, Wang JZ. Activation of glycogen synthase kinase-3 inhibits long term potentiation with synapse-associated impairments. J Neurosci. 2007, 27:12211–12220.
20. Wang JZ, Grundke-Iqbal I, Iqbal K. Glycosylation of microtubule-associated protein tau: an abnormal posttranslational modification in Alzheimer disease. Nat Med. 1996,2(8): 870-876.
在研项目
1.Tau蛋白异常聚积引起神经细胞退变的分子机制研究2018-01至 2020-12 NSFC重点项目
2. 内侧隔核-海马胆碱能环路损伤在阿尔茨海默病空间记忆障碍中的作用及机制 2017-01至 2019-12 NSFC神经环路集成项目
3.阿尔茨海默病神经慢性退变机制及危险因素研究 2016.09-2021.08 科技部重大基础研发项目
4. NSFC创新群体2018-01至 2020-12
5.治疗AD脑源性神经营养因子活性肽药物研发 湖北省科技厅2016-09-2019-08
科研获奖
1.Tau蛋白过度磷酸化机制及其在阿尔茨海默病神经元变性中的作用。国家自然科学奖 二等奖 第1完成人 2010
2.Tau蛋白过度磷酸化的机制及其对神经元生存命运的影响。高等学校自然科学奖 一等奖 第1完成人 2009
3.蛋白激酶在阿尔茨海默病tau蛋白过度磷酸化中的作用及应用价值。中华医学科技奖 二等奖 第1完成人 2008
4.糖原合酶激酶-3在tau蛋白磷酸化中作用及调节机制。湖北省自然科学奖 一等奖 第1完成人 2008
5.细胞骨架蛋白异常在老年性痴呆症发病中的作用及其临床意义。教育部提名国家科学技术奖自然科学奖 一等奖 第1完成人 2005
6.老年性痴呆骨架蛋白异常修饰机制的研究。 中华医学科技奖 一等奖 第1完成人 2002
