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病理生理学系
朱铃强

朱铃强,三级教授,博士生导师,中组部万人计划青年拔尖人才,教育部新世纪优秀人才支持计划获得者、耶鲁大学博士后、华中学者特聘岗、国际杂志Journal of Alzheimer’s Disease(影响因子3.9Senior Editor、全国百篇优秀博士论文提名奖获得者,湖北省杰出青年基金获得者,2016湖北省科协创新创业人才工程,华中科技大学中加神经疾病分子生物学联合平台中方负责人,华中科技大学首届学术前沿青年团队负责人,首届学术新人奖获得者。目前研究方向:阿尔茨海默病的早期防治措施研究。承担国家自然科学基金青年项目、面上项目、动物模型专项、重大计划培育项目、国际合作(中德,中加)、海外港澳台基金共10项,科技部重大国际合作专项一项、美国阿尔茨海默病协会(Alzheimer Association)新研究者基金一项。目前以通讯作者和第一作者发表SCI论文48篇,其中包括Nature NeuroscienceNeuronMol PsychiatryNature CommunicationsBiological PsychiatryCell Death & Differ.Mol TherapyJ Neurosci6篇)、Aging CellMol NeurobiolNeurobiol AgingJ Neurochem等国际知名杂志,长期担任国家自然科学基金委一审专家,意大利国家自然科学基金衰老组一组组长。

联系方式

基础医学院二号教学楼八楼803办公室

电话:13308657291

Emailzhulq@mail.hust.edu.cn

QQ: 307728280

工作简介

主要从事阿尔茨海默病(Alzheimer’s disease, AD)发病的分子机制及防治措施的研究。该病是一种高发于老龄人群的神经退行性疾病,AD患者的主要临床表现为学习记忆能力渐进性减退,从而给其生活带来了极大的不便,也给家庭和社会造成了极大的经济和精神负担。目前认为,AD早期突触可塑性的紊乱是引起AD患者学习记忆障碍的主要原因,但其机制和可能的保护措施暂不明了。申请人针对AD突触病变及神经环路异常的发生发展的机制展开了一系列的工作并取得了一定的科研成果,主要包括:
1利用光遗传学和转基因技术,首次发现内嗅皮层II层的岛细胞可以直接投射到海马CA1的小清蛋白(PV)阳性的抑制性神经元形成ECIIPN–CA1 PV神经环路,并且发现其功能在AD早期明显降低,从而引起CA1脑区兴奋/抑制失平衡并参与AD早期的学习记忆障碍;

2,系统研究了一系列miRNAAD发病中的作用,如miR-124可以明显下调Zif268的表达,进而抑制小鼠的学习记忆和社会交往能力;miR-218分子可以特异的作用于PTPa,而后者则可以特异性调控tau蛋白磷酸化相关的激酶GSK-3及酯酶PP2A的酪氨酸磷酸化,从而打破激酶和酯酶的平衡并且引起tau过度磷酸化和聚集的病变;

3,系统地研究并证明了糖原合酶激酶 3 激活在阿尔茨海默病突触病变形成中的重要作用,并阐明了其作用机理是通过磷酸化突触前 P/Q 型钙通道阻碍了突触前囊泡的释放,从而抑制长时程增强(LTP)的形成。并且针对糖原合酶激酶 3 激活探讨了一系列的保护措施。


发表论文(*通讯作者)

1. Li X, Chen W, Pan K, Li H, Pang P, Guo Y, Shu S, Cai Y, Pei L, Liu D, Afewerky HK, Tian Q, Zhu LQ*, Lu Y*. Serotonin receptor 2c-expressing cells in the ventral CA1 control attention via innervation of the Edinger-Westphal nucleus. Nat Neurosci. 2018 Aug 13.

2. Li K, Wei Q, Liu FF, Hu F, Xie AJ, Zhu LQ*, Liu D*. Synaptic Dysfunction in Alzheimer's Disease: Aβ, Tau, and Epigenetic Alterations. Mol Neurobiol. 2018 55:3021-3032.

3. Wang X, Liu D, Huang HZ, Wang ZH, Hou TY, Yang X, Pang P, Wei N, Zhou YF, Dupras MJ, Calon F, Wang YT, Man HY, Chen JG, Wang JZ, Hébert SS, Lu Y, Zhu LQ*. A Novel MicroRNA-124/PTPN1 Signal Pathway Mediates Synaptic and Memory Deficits in Alzheimer's Disease. Biol Psychiatry. 2018:83;395-405. (Highlight in this issue and commentary by Dr. Wang-Xia Wang)

4. Yang X, Yao C, Tian T, Li X, Yan H, Wu J, Li H, Pei L, Liu D, Tian Q, Zhu LQ, Lu Y. Synaptic mechanism in Alzheimer's disease: a selective degeneration of an excitatory synaptic pathway in the CA1 hippocampus that controls spatial learning and memory in Alzheimer's disease. Mol Psychiatry. 2018 Feb;23(2):167.(Image)

5. Yang X, Yao C, Tian T, Li X, Yan H, Wu J, Li H, Pei L, Liu D, Tian Q, Zhu LQ*, Lu Y*. A novel mechanism of a memory loss in Alzheimer’s disease mice via degeneration of entorhinal-CA1 synapses. Mol Psychiatry. 2018: 23(2):199-210. (IF=13.7)

6. Wang DQ, Fu P, Yao C, Zhu LS, Hou TY, Chen JG, Lu Y, Liu D*, Zhu LQ*. Long non-coding RNAs, novel culprits or bodyguards in neu-rodegenerative diseases. Molecular Therapy-Nucleic Acid. 2018, 10(2):269-276.

7. Zhu H, Yan H, Tang N, Li X, Pang P, Li H, Chen W, Guo Y, Shu S, Cai Y, Pei L, Liu D, Luo MH, Man H, Tian Q, Mu Y*, Zhu LQ*, Lu Y*. Impairments of spatial memory in an Alzheimer’s disease model via degeneration of hippocampal cholinergic synapses. Nat Commun. 2017, Nat Commun. 2017 Nov 22;8(1):1676.

8. Wu L, Meng J, Shen Q, Zhang Y, Pan S, Chen Z, Zhu LQ, Lu Y, Huang Y, Zhang G. Caffeine inhibits hypothalamic A(1)R to excite oxytocin neuron and ameliorate dietary obesity in mice. Nat Commun. 2017 Jun 27;8:15904.

9. Yang S, Jin H, Zhu Y, Wan Y, Opuku EN, Zhu LQ*, Hu B*. Diverse Functions and Mechanisms of Pericytes in Ischemic Stroke. Current Neuropharmacology, In press

10. Liu D, Tang H, Li XY, Deng MF, Wei N, Wang X, Zhou YF, Wang DQ, Fu P, Wang JZ, Hebert SS, Chen JG, Lu Y, Zhu LQ*. Targeting the HDAC2/HNF-4A/miR0101b/AMPK pathway rescues tauopathy and dendritic abnormalities in Alzheimer’s disease Molecular Therapy. 2017 Mar 1;25(3):752-764 (IF=6.938)

11. An TH, He QW, Xia YP, Chen SC, Baral S, Mao L, Jin HJ, Li YN, Wang MD, Chen JG, Zhu LQ*, Hu B*. MiR-181b Antagonizes Atherosclerotic Plaque Vulnerability Through Modulating Macrophage Polarization by Directly Targeting Notch1. Mol Neurobiol. 2016 Oct 8.

12. Shu S, Zhu HZ, Tang N, Chen W, Li X, Li H, Pei L, Liu D, Mu Y, Tian Q, Zhu LQ*, Lu Y*. Selective Degeneration of Entorhinal-CA1 Synapses in Alzheimer’s Disease via Activation of DAPK1. J Neurosci. 2016 Oct 19;36(42):10843-10852 (IF=5.9)

13. Liu YS, Dai X, Wu W, Yuan FF, Gu X, Chen JG, Zhu LQ*, Wu J*. The Association of SNAP25 Gene Polymorphisms in Attention Deficit/Hyperactivity Disorder: a Systematic Review and Meta-Analysis. Mol Neurobiol. 2017 Apr;54(3):2189-2200. (IF=5.3)

14. Xie AJ, Liu EJ, Huang HZ, Hu Y, Li K, Lu Y, Wang JZ*, Zhu LQ*. Cnga2 Knockout Mice Display Alzheimer's-Like Behavior Abnormities and Pathological Changes. Mol Neurobiol. 2016 Sep;53(7):4992-9.

15. Xiong YS, Liu FF, Liu D, Huang HZ, Wei N, Tan L, Chen JG, Man HY, Gong CX, Lu Y, Wang JZ, Zhu LQ*. Opposite effects of two estrogen receptors on tau phosphorylation regulation through disparate effects on the miR-218/PTPA pathway. Aging Cell, 2015, 14: 867–877.

16. Wang MD, Wang Y, Xia YP, Dai JW, Gao L, Wang SQ, Wang HJ, Mao L, Li M, Yu SM, Tu Y, He QW, Zhang GP, Wang L, Xu GZ, Xu HB, Zhu LQ*, Hu B*. High Serum MiR-130a Levels Are Associated with Severe Perihematomal Edema and Predict Adverse Outcome in Acute ICH. Mol Neurobiol. 2016 Mar;53(2):1310-21.

17. Li K, Liu FF, He CX, Huang HZ, Xie AJ, Hu F, Liu D, Wang JZ*, Zhu LQ*. Olfactory Deprivation Hastens Alzheimer-Like Pathologies in a Human Tau-Overexpressed Mouse Model via Activation of cdk5. Mol Neurobiol. 2016 Jan;53(1):391-401.

18. 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 & Differentiation. 2015 Apr;22(4):583-96.

19. Hu J, Huang HZ, Wang X, Xie AJ, Wang X, Liu D, Wang JZ*, Zhu LQ*. Glycogen synthase kinase-3 links the olfactory deficit to hippocampal impairments. Mol Neurobiol. 2015 Dec;52(3):1601-17.

20. Liu DY, Shen XM, Yuan FF, Guo OY, Zhong Y, Chen JG, Zhu LQ* Wu J*. The physiology of BDNF and its relationship with ADHD. Mol Neurobiol. 2015 Dec;52(3):1467-76.

21. Pei L, Shang Y, Jin H, Wang S, Wei N, Yan H, Wu Y, Yao C, Wang X, Zhu LQ*, Lu Y*. DAPK1-p53 Interaction Converges Necrotic and Apoptotic Pathways of Ischemic Neuronal Death. J Neurosci. 2014 May 7;34(19):6546-56.

22. Chen Y, Wang B, Liu D, Li JJ, Xue Y, Sakata K, Zhu LQ, Heldt SA, Xu H, Liao FF. Hsp90 chaperone inhibitor 17-AAG attenuates Aβ-induced synaptic toxicity and memory impairment. J Neurosci. 2014 Feb 12;34(7):2464-70.

23. Wang X, Wang LP, Tang H, Shan WY, Wang X, Liu D, Wu YY, Tian Q, Wang JZ*, Zhu LQ*. Acetyl-l-carnitine rescues scopolamine-induced memory deficits by restoring insulin-like growth factor II via decreasing p53 oxidation. Neuropharmacology. 2014, 76(A) :80-87.

24. Wu YY, Wang X, Tan L, Liu D, Liu XH, Wang Q, Wang JZ*, Zhu LQ*. Lithium Attenuates Scopolamine-Induced Memory Deficits with Inhibition of GSK-3β and Preservation of Postsynaptic Components. J Alzheimers Dis. 2013, 37(3):515-527.

25. Tang H, Shen N, Jin HJ, Liu D*, Miao X*, Zhu LQ*. GSK-3β polymorphism discriminates bipolar disorder and schizophrenia: a systematic meta-analysis. Molecular Neurobiology. 2013,48(3):404-411.

26. Xiong YS, Wang DL, Tan L, Wang X, Chen LM, Gong CX, Wang JZ*, Zhu LQ*. Inhibiton of glycogen synthase kinase-3 reverses tau hyperphosphorylation induced by Pin1 downregulation. CNS & Neurological Disorders - Drug Targets. 2013, 12(3):436-443.

27. Zhao K, Wen R, Wang X, Pei L, Yang Y, Shang Y, Bazan N, Zhu LQ*, Tian Q*, Lu Y*. EPAC Inhibition of SUR1 Receptor Increases Glutamate Release and Seizure Vulnerability. J Neurosci. 2013,33(20):8861-8865. (IF=7.271)

28. Peng CX, Hu J, Liu D, Hong XP, Wu YY, Zhu LQ*, Wang JZ*. Disease-modified GSK-3b intervention by melatonin arrests the pathology and memory deficits in Alzheimer’s animal model. Neurobiology of Aging. 2013, 34(6):1555-1563. (IF=6.189)

29. Qu M, Jiang J, Liu XP, Tian Q, Chen LM, Yin G, Liu D, Wang JZ*, Zhu LQ*. Reduction and the intracellular translocation of EphB2 in Tg2576 mice and the effects of b-amyloid. Neuropathology and Applied Neurobiology. 2013 Oct;39(6):612-22. (IF=4.837)

30. Zhong R, Yang B, Tang H, Zou L, Song R, Zhu LQ*, Miao XP*. Meta-analysis of the association between DCDC2 polymorphisms and risk of Dyslexia. Molecular Neurobiology. 2013;47(1):435-442. (IF=5.735)

31. Wang X, Wang ZH, Wu YY, Tang H, Tan L, Wang X, Gao XY, Xiong YS, Liu D*, Wang JZ, Zhu LQ*. Melatonin attenuates scopolamine-induced memory/synaptic disorder by rescuing EPACs/miR-124/Egr1 pathsway. Molecular Neurobiology. 2013;47(1):373-381. (IF=5.735)

32. Wang SH, Liao XM, Liu D, Hu J, Yin YY, Wang JZ*, Zhu LQ*. NGF Promotes Long-term Memory Formation by Activating Poly(ADP-ribose)polymerase-1. Neuropharmacology. 2012;63(6):1085-1092 (IF=4.8)

33. Wu J, Xiao H, Sun H, Zou L, Zhu LQ*. Role of dopamine receprots in ADHD: a systematic meta-analysis. Molecular Neurobiology. 2012; 45(3):605-20. (IF=5.735)

34. 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 WH, Zhu LQ*, Wang JZ*, Lu Y*. EPAC Null Mutation Impairs Learning and Social Interactions via Aberrant Regulation of miR-124 and Zif268 Translation. Neuron, 2012;73(4):774-788. (IF=14.027)

35. Liao K, Liu D, Zhu LQ*. Enriched odor exposure decrease tau phosphorylation in the rat hippocampus and cortex. Neurosci Lett. 2012;507(1):22-26. (IF=2.055)

36. Hu J, Wang X, Liu D, Wang Q, Zhu LQ*. Olfactory deficits induce neurofilament hyperphosphorylation. Neurosci Lett. 2012; 506(2):180-183. (IF=2.055)

37. Zhou P, Chen Z, Zhao N, Liu D, Hu J, Guo ZY, Wang Q, Wang JZ*, Zhu LQ*. Acetyl-L-Carnitine attenuates homocysteine-induced Alzheimer-like histopathological and behavioral abnormalities. Rejuvenation Research. 2011, 14(6): 669-679. (IF=4.225)

38. Jiang X, Tian Q, Wang Y, Zhou XW, Xie JZ, Wang JZ, Zhu LQ*. Acetyl-L-Carnitine ameliorates spatial memory deficits induced by inhibition of phosphoinositol-3 kinase and protein kinase C. J Neurochem. 2011;118(5):864-878.(IF=4.337)

39. Chen LM, Xiong YS, Kong FL, Qu M, Wang Q, Chen XQ, Wang JZ*, Zhu LQ*. Neuroglobin attenuates Alzheimer-like tau hyperphosphorylation by activating Akt signaling. J Neurochem. 2012 Jan;120(1):157-64 (IF=4.337)

40. Liu D, Zheng HY, Luo ZZ, Wang Q, Zhu LQ*. Effect of PP-2A on neurite outgrowth in neuronal cells. In Vitro Cell Dev-AN, 2010, 46(8): 702-707 (IF=1.312)

41. Zhu LQ, Liu D, Hu J, Cheng J, Wang SH, Wang Q, Wang F, Chen JG, Wang JZ. GSK-3b inhibits presynaptic vesicle exocytosis by phosphorylating P/Q-type calcium channel and interrupting SNARE complex formation. J Neurosci. 2010;30(10):3624-33. (IF:7.49)

42. Zhu LQ, Zheng HY, Peng CX, Liu D, Li HL, Wang Q, Wang JZ. Protein phosphatase 2A facilitates functional axonogenesis by dephosphorylating CRMP2. J Neurosci. 2010;30(10):3839-48. (IF:7.49)

43. Yin YY, Liu H, Liu Z, Cong XB, Wang Q, Wang JZ*, Zhu LQ*. Acetyl-L-carnitine attenuates okadaic acid induced tau hyperphosphorylation and spatial memory impairment in rats. J Alzheimer’s Disease 2010;19(2):735-46. (IF=5.0)

44. Shi HR, Zhu LQ*, Wang SH, Liu XA, Tian Q, Zhang Q, Wang Q, Wang JZ*. (2008). 17 β-estradiol attnuates glycogen synthase kinase-3β activation and tau hyperphosphorylation in Akt-independent manner. J Neural Transmission 115(6):879-888. (IF:2.938)

45. Liu XA, Zhu LQ*, Zhang Q, Shi HR, Wang SH, Wang Q, Wang JZ*. (2008). Estradiol attenuates tau hyperphosphorylation induced by upregulation of protein kinase-A. Neurochemical Res 2008 Sep;33(9):1811-20. (IF:2.18)

46. Zhu LQ, Wang SH, Liu D, Yin YY, Tian Q, Wang XC, Wang Q, Chen JG, Wang JZ (2007). Activation of glycogen synthase kinase-3 inhibits long term potentiation with synapse-associated impairments. J Neurosci 27:12211-12220. (IF:7.49)

47. Wang SH, Zhu LQ, Wang Q, et al. (2007). Inhibition of Melatonin Biosynthesis Induces Neurofilament Hyperphosphorylation with Activation of Cyclin-dependent Kinase 5. Neurochem Res 32(8):1329-1335. (IF:2.18)

48. Zhu LQ, Wang SH, Ling ZQ, et al. (2004). Effect of inhibiting melatonin biosynthesis on    spatial memory retention and tau phosphorylation in rat. J Pineal Res 37 (2):71-77. (IF:4.228)



承担项目

2008年,国家自然科学基金青年基金,30800342,糖原合酶激酶3在阿尔茨海默病突触病变中的作用和机制,20万元,负责人 2009.1.1-2011.12.31

2009年,国家自然科学基金面上基金,30971478,雌激素受体beta在衰老相关记忆障碍中的作用和机制,31万元,负责人 2010.1.1-2012.12.31

2009年,华中科技大学首届学术新人奖人才基金,20万,负责人

2010年,教育部新世纪优秀人才支持计划,NCET-10-0421,神经细胞粘附分子唾液酸化失调引起阿尔茨海默病突触病变的分子机理,50万,负责人 2011.5-2014.4

2011年,美国阿尔茨海默协会基金,NIRG-11-205737Role of EphB2

signal in tau pathology in Alzheimer's Disease10万美金,负责人(目前中国获得该基金的只有三人) 2011.10-2013.9

2011年,国家自然科学基金重大计划,91132725, 嗅觉环境变化对内嗅皮层-海马环路功能的影响及在阿尔茨海默病样记忆障碍中的作用80万元,负责人 2012.1.1-2014.12.31

2012年,中国科技部-加拿大国际合作专项基金,2011DFG33250,运用新型基因技术探索糖原合酶激酶3在脑功能和疾病中作用的合作研究,170万元,负责人 2012.4-2015.3

2013年,国家自然科学基金委员会(NSFC)与加拿大魁北克医学研究基金会(FRQS)合作研究项目,81361120245,整体水平研究EPAC/miR-124信号通路在阿尔兹海默发病中的作用和机制,100万元,负责人 2013.1.-2015.12.31

2014年,湖北省杰出青年基金, 2014CFA017, 组蛋白去乙酰化酶2调控AD脑内淀粉样蛋白生成和tau病变的机制,10万元,负责人,2014.1-2016.12.

2014,  国家自然科学基金委员会海外及港澳学者合作研究基金, 81428009, 智障相关蛋白KIAA202在神经元发育及突触形成中的作用,20万元,第一参与人(境内负责人),2015.1-2016.12.

2015年,国家自然科学基金面上项目,31571039,长链非编码RNA AK036689在阿尔茨海默病早期海马突触环路功能障碍中的作用,76.8万元,负责人,2016.1.1-2019.12.31.

2015年,国家特支计划青年拔尖人才专项基金,190万元

2015年,华中科技大学首届青年学术团队专项基金,60万元/年持续资助

2016年,国家自然科学基金重大计划,91632114, 长链非编码mSYT-AS异常在阿尔茨海默病ECIIPN-CA1PV环路功能障碍中作用研究,60万元,负责人 2017.1.1-2019.12.31

2017年,国家自然科学基金面上项目动物模型专项,81771150,运用光遗传可调控性转基因小鼠模型研究基底前脑-海马DG胆碱能神经环路损伤在阿尔茨海默病早期模式分别障碍中的作用,80万元,负责人,2018.1.1-2021.12.31

2017年,国家自然科学基金创新群体项目,31721002,记忆神经环路研究群体,1050万元,参与人,2018.1.1-2023.12.31

2017年,国家自然科学基金委员会(NSFC)与德国科学基金会(DFG)合作研究项目,81761138043,微小RNA调节网络在阿尔茨海默病神经环路功能障碍中的作用(MiRNetAD)180万元,负责人,2018.1.1-2020.12.31

2018,  国家自然科学基金委员会海外及港澳学者合作研究基金延续性项目, 81829002, miR-138/Nrgn信号通路在智障相关蛋白KIDLIA缺失所致自闭症样社交异常及突触紊乱中的作用和机理,180万元,第一参与人(境内负责人),2019.1-2022.12.


专利

朱铃强;王雄;王玉田;刘丹;黄和周。一种防治老年痴呆的药物。专利号:2014106681340,授权日,2017.6.16


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