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病理生理学系
王建枝

王建枝教授,教育部长江学者奖励计划特聘教授,国家杰出青年科学基金获得者、国家教学名师、全国师德标兵、全国优秀科技工作者、华中科技大学伯乐奖、研究生最喜爱导师奖获得者,教育部神经系统重大疾病重点实验室主任,教育部神经系统重大疾病创新团队牵头人,国家重点学科病理学与病理生理学学科负责人。现为华中科技大学教授,博士生导师,兼任同济医学院基础医学院副院长,病理生理学系主任,中国病理生理学会副理事长,湖北省暨武汉市病理生理学会理事长等。1978年同济医学院临床医学专业毕业后留校任生物化学教师,1992年获意大利外交部奖学金在siena大学作访问学者,1993年-1996年在美国纽约大学基础研究所从事博士后研究,1996年回母校病理生理学系工作至今。

研究方向:老年性痴呆症的发病机制和防治策略的研究

主要学术贡献:(1)基于对老年性痴呆症的系统研究和新发现,在国际上首次提出了老年性痴呆症的神经退行性变涉及主动、有序分子调控的学术思想及“退行性变性死亡”的新概念,揭示了老年性痴呆症神经退行性变的本质。(2)创新建立了脑脊液微量磷酸化骨架蛋白的检测技术,为老年性痴呆症的临床诊断奠定了技术基础。(3)阐述了糖原合酶激酶-3b在tau蛋白过度磷酸化中的关键作用和调节机制,系列研究结果为糖原合酶激酶-3b作为老年性痴呆症药物开发的靶点提供了科学依据。(4)发现磷酸酯酶-2a是使异常tau蛋白去磷酸化的关键磷酸酯酶,建立了相关研究实验模型。发表sci论文100余篇,被正面引用1400余次。相关研究成果提升了我国在ad领域的国际影响力。

科研成果:相关研究结果获教育部自然科学奖一等奖(2项)、中华医学科技奖一等奖、湖北省自然科学奖一等奖,有关tau蛋白的研究结果于2010年获国家自然科学奖二等奖。

科研课题:正在主持nsfc神经环路重大研究计划重点项目、中加合作重点项目、面上项目、美国老年性痴呆协会研究项目、美国nih firca基金等;是获得美国nih firca基金的第一位中国学者、获美国li基金等。

教学和人才培养:主编国家规划教材《病理生理学》中、英文版,主讲课程《病理生理学》2004年获国家精品课程。培养的青年教师4人获教育部新世纪人才,10余人获得国家自然科学基金资助,学生30余人次获国外资助参加ad国际会议,培养的博士研究生分别获2009年、2008年、2006年和2003年全国百篇优秀博士论文提名奖。

部分科研论文

1. xiong y, jing xp, zhou xw, wang xl, yang y, sun xy, qiu m, cao fy, lu ym, liu r, wang jz. zinc induces protein phosphatase 2a inactivation and tau hyperphosphorylation through src dependent pp2a (tyrosine 307) phosphorylation. neurobiol aging. 2012 aug 11. [epub ahead of print]

2. 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 pathway. molneurobiol. 2012 oct 7. [epub ahead of print]

3. liu xa, song j, jiang q, wang q, tian q,wang jz. expression of the hyperphosphorylated tau attenuates er stress-induced apoptosis with upregulation of unfolded protein response. apoptosis. 2012 oct;17(10):1039-49.

4. li xh, zhou xw, wang jz. ages induce alzheimer-like tau pathology and memory deficit via rage-mediated gsk-3 activation. neurobiol aging. 2012 jul;33(7):1400-10

5. li xh, xie jz, jiang x, lv bl, cheng xs, du ll, zhang jy, wang jz, zhou xw.methylglyoxal induces tau hyperphosphorylation via promoting ages formation.neuromolecular med. 2012 jul 14. [epub ahead of print]

6. wang sh, liao xm, liu d, hu j, yin yy,wang jz, zhu lq. ngf promotes long-term memory formation by activatingpoly(adp-ribose)polymerase-1.neuropharmacology.2012nov;63(6):1085-92.

7. yao xq, li xc, zhang xx, yin yy, liu b, luo dj, wang q,wang jz, liu gp. glycogen synthase kinase-3β regulates leucine-309 demethylation of proteinphosphatase-2a via ppmt1 and pme-1. febs lett. 2012 jul 30;586(16):2522-8.

8. liu xp, zheng hy, qu m, zhang y, cao fy, wang q, ke d, liu gp, wang jz. upregulation of astrocytes protein phosphatase-2a stimulates astrocytes migration via inhibiting p38 mapk in tg2576 mice. glia. 2012 sep;60(9):1279-88.

9. wang jz, xia yy, grundke-iqbal i, iqbal k. abnormal hyperphosphorylation of tau: sites, regulation, and molecular mechanism of neurofibrillary degeneration. j alzheimer’s dis. 2012 jun 18. [epub ahead of print]

10. liu zc, fu zq, song j, zhang jy, wei yp, chu j, han l, qu n, wang jz, tian q. bip enhanced the association of gsk-3β with tau during er stress both in vivo andin vitro. j alzheimer’s dis. 2012;29(4):727-40.

11. chen nn, luo dj, yao xq, yu c, wang y, wang q, wang jz, liu gp. pesticidesinduce spatial memory deficits with synaptic impairments and an imbalanced tauphosphorylation in rats. j alzheimer’sdis.2012;30(3):585-94.

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 tauhyperphosphorylation 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. chen p,tian q , baek sj, shang x, park a, liu z, yao x, wang jz*,wang x, cheng y, peng j, shen ag, hu j*. laserramandetectionofplateletasa non-invasive approachforearlyanddifferentialdiagnosis of alzheimer’s disease. laser physlett. 2011, laser physics letters. 2011 july; 8(7) 547–552.

16. zhou p, chen z, zhao n, liu d, guo zy, tan l, hu j, wang q, wang jz, zhu lq. acetyl-l-carnitine attenuates homocysteine-induced alzheimer-like histopathological and behavioral abnormalities. rejuvenation res. 2011dec;14(6):669-79.

17. wei w, liu yh, zhang ce, wang q, wei z, mousseau dd,wang jz, tian q, liu gp.folate/vitamin-b12 prevents chronichyperhomocysteinemia-induced tau hyperphosphorylation and memory deficits in aged rats. j alzheimer’s dis.2011;27(3):639-50.

18. jiang x, tian q, wang y, zhou xw, xie jz,wang jz, zhu lq. acetyl-l-carnitineameliorates spatial memory deficits induced by inhibition of phosphoinositol-3kinase and protein kinase c. j neurochem. 2011sep;118(5):864-78.

19. yao xq, zhang xx, yin yy, liu b, luo dj, liu d, chen nn, ni zf, wang x, wangq,wang jz, liu gp. glycogen synthase kinase-3β regulates tyr307 phosphorylation of protein phosphatase-2a via protein tyrosine phosphatase 1b but not src. biochem j. 2011 jul 15;437(2):335-44.

20. 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.

21. yin g, li ly, qu m, luo hb,wang jz, zhou xw. upregulation of akt attenuates amyloid-β-induced cell apoptosis. j alzheimer’s dis. 2011;25(2):337-45.

22. yu g, li y, tian q, liu r, wang q,wang jz, wang x. berberine attenuates calyculin a-induced cytotoxicity and tau hyperphosphorylation in hek293 cells. j alzheimer’s dis. 2011;24(3):525-35.

23. hong xp, peng cx, wei w, tian q, liu yh, cao fy, wang q, wang jz. relationship of adult neurogenesis with tau phosphorylation and gsk-3β activityinsubventricular zone. neurochem res. 2011 feb;36(2):288-96.

24. 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.

25. zhu lq, liu d, hu j, cheng j, wang sh, wang q, wang f, chen jg, and wang jz. gsk-3 inhibits presynaptic vesicle exocytosis by phosphorylating p/q-type calcium channel and interrupting snare complex formation. j neurosci. 2010,30:3849-3855.

26. yang yj, wu pf, long lh, yu df, wu wn, hu zl, fu h, xie n, jin y, ni l, wang jz, wang f, chen jg. reversal of aging-associated hippocampal synaptic plasticity deficits by reductants via regulation of thiol redox and nmda receptor function. aging cell. 2010,9(5):709-21.

27. hong xp, peng cx, wei w, tian q, liu yh, yao xq, zhang y, cao fy, wang q,wang jz. essential role of tau phosphorylation in adult hippocampal neurogenesis. hippocampus. 2010, 20(12):1339-49.

28. fu zq, yang y, song j, jiang q, liu zc, wang q, zhu lq, wang jz, tian q. licl attenuates thapsigargin-induced tau hyperphosphorylation by inhibiting gsk-3beta in vivo and in vitro. j alzheimer’s dis. 2010 aug 6. [epub ahead of print]

29. wang hh, li hl, liu r, zhang y, liao k, wang q, wang jz, liu sj. tau overexpression inhibits cell apoptosis with the mechanisms involving multiple viability-related factors. j alzheimer’s dis. 2010,21(1):167-79.

30. chen x, wu j, hua d, shu k, wang jz, li l, lei t. the c-jun n-terminal kinase inhibitor sp600125 is neuroprotective in amygdala kindled rats. brain res. 2010 oct 21;1357:104-14.

31. zhu wz, zhong wd, wang w, zhan cj, wang cy, qi jp, wang jz, lei t.quantitative mr phase-corrected imaging to investigate increased brain iron deposition of patients with alzheimer disease. radiology. 2009 nov;253(2):497-504

32. yao z, guo z, yang c, tian q, gong cx, liu g, wang jz. phenylbutyric acid prevents rats from electroconvulsion-induced memory deficit with alterations of memory-related proteins and tau hyperphosphorylation. neuroscience. 2010 jun 30;168(2):405-15.

33. wang zf, yin j, zhang y, zhu lq, tian q, wang xc, li hl, wang jz. overexpression of tau proteins antagonizes amyloid-beta-potentiated apoptosis through mitochondria-caspase-3 pathway in n2a cells. j alzheimer’s dis.2010;20(1):145-57.

34. liu xa, liao k, liu r, wang hh, zhang y, zhang q, wang q, li hl, tian q, wang jz. tau dephosphorylation potentiates apoptosis by mechanisms involving a failed dephosphorylation/activationof bcl-2. j alzheimer’s dis. 2010;19(3):953-62.

35. yin yy, liu h, cong xb, liu z, wang q, wang jz, zhu lq. acetyl-l-carnitine attenuates okadaic acid induced tau hyperphosphorylation and spatial memoryimpairment in rats. j alzheimer’s dis. 2010;19(2):735-46.

36. liu xa, liao k, liu r, wang hh, zhang y, zhang q, wang q, li hl, tian q, wang jz. tau dephosphorylation potentiates apoptosis with the mechanisms involving afailed dephosphorylation/activation of bcl-2. j alzheimer’s dis. [epub ahead of print]

37. yin yy, liu h, cong xb, liu z, wang q, wang jz, zhu lq. acetyl-l-carnitine attenuates okadaic acid induced tau hyperphosphorylation and spatial memoryimpairment in rats. j alzheimer’s dis. 2009 nov 5.

38. zhang ce, wei w, liu yh, peng jh, tian q, liu gp, zhang y, wang jz*. hyperhomocysteinemia increases beta-amyloid by enhancing expression of gamma-secretase and phosphorylation of amyloid precursor protein in rat brain. am j pathol. 74(4):1481-1491,2009,

39. hong xp, peng cx, wei w, tian q, liu yh, yao xq, zhang y, cao fy, wang q, wang jz*. essential role of tau phosphorylation in adult hippocampal neurogenesis. hippocampus. 2009 oct 8.

40. tian q, zhang jx, zhang y, wu f, tang q, wang c, shi zy, zhang jh, liu s, wang y, zhang q, wang jz*. biphasic effects of forskolin on tau phosphorylation and spatial memory in rats. j alzheimer’s dis. 2009;17(3):631-42.

41. zhang y, tian q, zhang q, zhou x, liu s,wang jz*. hyperphosphorylation of microtubule-associated tau protein plays dual role in neurodegeneration and neuroprotection. pathophysiology. 2009 oct;16(4):311-6.

42. ling zq, tian q, wang l, fu zq, wang xc, wang q, wang jz*. constant illumination induces alzheimer-like damages with endoplasmic reticulum involvement and the protection of melatonin. j alzheimer’s dis. 2009;16(2):287-300.

43. zhang jy, peng c, shi h, wang s, wang q,wang jz*. inhibition of autophagy causes tau proteolysis by activating calpain in rat brain. j alzheimer’s dis. 2009;16(1):39-47.

44. wang y, zhang jx, du xx, zhao l, tian q, zhu lq, wang sh, wang jz*. temporalcorrelation of the memory deficit with alzheimer-like lesions induced by activation of glycogen synthase kinase-3. j neurochem. 2008 sep;106(6):2364-74.

45. wang jz*, liu f. microtubule-associated protein tau in development, degeneration and protection of neurons. progneurobiol. 2008 jun;85(2):148-75.

46. liu yh, wei w, yin j, liu gp, wang q, cao fy, wang jz*. proteasome inhibition increases tau accumulation independent of phosphorylation. neurobiol aging. 2009 dec;30(12):1949-61.

47. liu xa, zhu lq, zhang q, shi hr, wang sh, wang q,wang jz*. estradiol attenuates tau hyperphosphorylation induced by upregulation of protein kinase-a. neurochem res. 2008 sep;33(9):1811-20.

48. zhang yj, xu yf, liu xh, li d, yin j, liu yh, chen xq, wang jz*. carboxyl terminus of heat-shock cognate 70-interacting protein degrades tau regardless its phosphorylation status without affecting the spatial memory of the rats. j neuraltransm. 2008;115(3):483-91.

49. liu r, zhou xw, tanila h, bjorkdahl c, wang jz*, guan zz, cao y, gustafsson ja, winblad b, pei jj. phosphorylated pp2a (tyrosine 307) is associated with alzheimer neurofibrillary pathology. j cell mol med. 2008 jan-feb;12(1):241-57.

50. zhang ce, tian q, wei w, peng jh, liu gp, zhou xw, wang q, wang dw, wang jz*. homocysteine induces tau phosphorylation by inactivating protein phosphatase 2a in rat hippocampus. neurobiol aging. 2008 nov;29(11):1654-65.

51. liu gp, zhang y, yao xq, zhang ce, fang j, wang q, wang jz*. activation of glycogen synthase kinase-3 inhibits protein phosphatase-2a and the underlying mechanisms. neurobiol aging. 2008 sep;29(9):1348-58.

52. zhu lq, wang sh, yin yy, liu d, zheng hy, shi hr, tian q, wang xc, wang q, guo l,wang jz*. activation of glycogen synthase kinase-3 inhibits long term potentiation with synapse-associated impairments. j neurosci. 2007, 27:12211–12220.

53. fang j, liu r, tian q, hong xp, wang sh, cao fy, pan xp,wang jz*. dehydroevodiamine attenuates calyculin a-induced tau hyperphosphorylation in rat brain slices. actapharmacol sin. 2007 nov;28(11):1717-23.

54. ren qg, liao xm, chen xq, liu gp,wang jz*. effects of tau phosphorylation on proteasome activity. febs lett. 2007 apr 3;581(7):1521-8.

55. 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. procnatlacadsci u s a. 2007 feb 27;104(9):3591-6.

56. wang jz*, grundke-iqbal i, iqbal k. kinases and phosphatases and tau sites involved in alzheimer neurofibrillary degeneration. eur j neurosci. 2007 jan;25(1):59-68.

57. yin j, liu yh, xu yf, zhang yj, chen jg, shu bh, wang jz*. melatonin arrests peroxynitrite-induced tau hyperphosphorylation and the overactivation of protein kinases in rat brain. j pineal res. 2006 sep;41(2):124-9.

58. zhang yj, xu yf, liu yh, yin j, li hl, wang q, wang jz*. peroxynitrite induces alzheimer-like tau modifications and accumulation in rat brain and its underlying mechanisms. faseb j. 2006 jul;20(9):1431-42.

59. wang d, qian l, xiong h, liu j, neckameyer ws, oldham s, xia k, wang jz, bodmer r, zhang z. antioxidants protect pink1-dependent dopaminergic neurons in drosophila. procnatlacadsci u s a. 2006 sep 5;103(36):13520-5.

60. wang zf, li hl, li xc, zhang q, tian q, wang q, xu h, wang jz*. effects of endogenous beta-amyloid overproduction on tau phosphorylation in cell culture. j neurochem. 2006 aug;98(4):1167-75.

61. wang yp, wang xc, tian q, yang y, zhang q, zhang jy, zhang yc, wang zf, wang q, li h, wang jz*. endogenous overproduction of beta-amyloid induces tau hyperphosphorylation and decreases the solubility of tau in n2a cells. j neural transm. 2006 nov;113(11):1723-32.

62. ren qg, liao xm, wang zf, qu zs,wang jz*. the involvement of glycogensynthase kinase-3 and protein phosphatase-2a in lactacystin-induced tau accumulation. febs lett. 2006 may 1;580(10):2503-11.

63. zhang y, li hl, wang dl, liu sj, wang jz*. a transitory activation of protein kinase-a induces a sustained tau hyperphosphorylation at multiple sites in n2a cells-imply a new mechanism in alzheimer pathology. j neural transm. 2006 oct;113(10):1487-97.

64. wang jz*, wang zf. role of melatonin in alzheimer-like neurodegeneration. actapharmacol sin. 2006 jan;27(1):41-9. review.

65. zhang yj, xu yf, liu yh, yin j, wang jz*. nitric oxide induces tau hyperphosphorylation via glycogen synthase kinase-3beta activation. febs lett. 2005 nov 7;579(27):6230-6.

66. zhu lq, wang sh, ling zq, wang q, hu mq,wang jz*. inhibition of melatonin biosynthesis activates protein kinase a and induces alzheimer-like tau hyperphosphorylation in rats. chin med sci j. 2005 jun;20(2):83-7.

67. liu r, pei jj, wang xc, zhou xw, tian q, winblad b, wang jz*. acute anoxia induces tau dephosphorylation in rat brain slices and its possible underlying mechanisms. j neurochem. 2005 sep;94(5):1225-34.

68. wang hh, zhang ah, zhu lq, wang q, wang jz*. overexpression of dishevelled-1 attenuates wortmannin-induced hyperphosphorylation of cytoskeletal proteins in n2a cell. actapharmacol sin. 2005 jun;26(6):679-84.

69. xu gg, deng yq, liu sj, li hl, wang jz*. prolonged alzheimer-like tauhyperphosphorylation induced by simultaneous inhibition of phosphoinositol-3 kinase and protein kinase c in n2a cells. actabiochimbiophys sin (shanghai). 2005 may;37(5):349-54.

70. zhang yj, xu yf, chen xq, wang xc, wang jz*. nitration and oligomerization of tau induced by peroxynitrite inhibit its microtubule-binding activity. febs lett. 2005 apr 25;579(11):2421-7.

71. deng yq, xu gg, duan p, zhang q, wang jz*. effects of melatonin on wortmannin-induced tau hyperphosphorylation. actapharmacol sin. 2005 may;26(5):519-26..

72. yan wh, cao md, liu jr, xu y, han xf, xing y,wang jz*. effects of egf and bfgf on expression of microtubule-associated protein tau and map-2 mrna in human umbilical cord mononuclear cells. cell biol int. 2005 feb;29(2):153-7.

73. ruben gc, wang jz, iqbal k, grundke-iqbali.paired helical filaments (phfs) are a family of single filament structures with a common helical turn period: negatively stained phf imaged by tem and measured before and after sonication, deglycosylation, and dephosphorylation. microsc res tech. 2005 jul;67(3-4):175-95.

74. li xc, wang zf, zhang jx, wang q, wang jz*. effect of melatonin on calyculin a-induced tau hyperphosphorylation. eur j pharmacol. 2005 mar 7;510(1-2):25-30.

75. 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. sheng li xuebao. 2005 feb 25;57(1):7-12.

76. hu zh, wang xc, li ly, liu ml, liu r, ling z, tian q, tang xw, wu yg, wang jz*. correlation of behavior changes and bold signal in alzheimer-like rat model. actabiochimbiophys sin (shanghai). 2004 dec;36(12):803-10.

77. xu yf, zhang yj, zhang ah, zhang q, wu t, wang jz*. attenuation of okadaic acid-induced hyperphosphorylation of cytoskeletal proteins by heat preconditioning and its possible underlying mechanisms. cell stress chaperones. 2004; 9(3):304-12.

78. liu sj, zhang jy, li hl, fang zy, wang q, deng hm, gong cx, grundke-iqbal i, iqbal k, wang jz*. tau becomes a more favorable substrate for gsk-3 when it is prephosphorylated by pka in rat brain. j biol chem. 2004 nov 26; 279(48):50078-88.

79. zhang jy, liu sj, li hl, wang jz*. microtubule-associated protein tau is a substrate of atp/mg(2+)-dependent proteasome protease system. j neural transm. 2005 apr;112(4):547-55.

80. zhu lq, wang sh, ling zq, wang dl, wang jz*. effect of inhibiting melatonin biosynthesis on spatial memory retention and tau phosphorylation in rat. j pineal res. 2004 sep;37(2):71-7.

81. wang dl, ling zq, cao fy, zhu lq, wang jz*. melatonin attenuatesisoproterenol-induced protein kinase a overactivation and tauhyperphosphorylation in rat brain. j pineal res. 2004 aug;37(1):11-6.

82. tian q, lin zq, wang xc, chen j, wang q, gong cx, wang jz*. injection of okadaic acid into the meynert nucleus basalis of rat brain induces decreased acetylcholine level and spatial memory deficit. neuroscience. 2004;126(2):277-84.

83. liu sj, zhang ah, li hl, wang q, deng hm, netzer wj, xu h, wang jz*. overactivation of glycogen synthase kinase-3 by inhibition of phosphoinositol-3 kinase and protein kinase c leads to hyperphosphorylation of tau and impairment of spatial memory. j neurochem. 2003 dec;87(6):1333-44.

84. liu sj, fang zy, yang y, deng hm, wang jz*. alzheimer-like phosphorylation of tau and neurofilament induced by cocaine in vivo. actapharmacol sin. 2003 jun;24(6):512-8.

85. sun l, liu sy, zhou xw, wang xc, liu r, wang q, wang jz*. inhibition of protein phosphatase 2a- and protein phosphatase 1-induced tau hyperphosphorylation and impairment of spatial memory retention in rats. neuroscience. 2003;118(4):1175-82.

86. gong cx, wang jz, iqbal k, grundke-iqbal i. inhibition of protein phosphatase 2a induces phosphorylation and accumulation of neurofilaments in metabolically active rat brain slices. neuroscilett. 2003 apr 10;340(2):107-10

87. iqbal k, alonso adel c, el-akkad e, gong cx, haque n, khatoon s, pei jj, tsujio i,wang jz, grundke-iqbal i. significance and mechanism of alzheimer neurofibrillary degeneration and therapeutic targets to inhibit this lesion. j molneurosci. 2002 aug-oct;19(1-2):95-9. review.

88. liu sj, wang jz*. alzheimer-like tau phosphorylation induced by wortmannin in vivo and its attenuation by melatonin. actapharmacol sin. 2002 feb;23(2):183-7.

89. hu yy, he ss, wang xc, duan qh, khatoon s, iqbal k, grundke-iqbal i, wang jz*. elevated levels of phosphorylated neurofilament proteins in cerebrospinal fluid of alzheimer disease patients. neuroscilett. 2002 mar 8;320(3):156-60.

90. wang j, tung yc, wang y, li xt, iqbal k, grundke-iqbal i. hyperphosphorylation and accumulation of neurofilament proteins in alzheimer disease brain and in okadaic acid-treated sy5y cells. febs lett. 2001 oct 19;507(1):81-7.

91. cheng ly, wang jz, gong cx, pei jj, zaidi t, grundke-iqbal i, iqbalk.multiple forms of phosphatase from human brain: isolation and partial characterization of affi-gel blue nonbinding phosphatase activities. neurochem res. 2001 apr;26(4):425-38.

92. iqbal k, alonso ad, gondal ja, gong cx, haque n, khatoon s, sengupta a, wang jz, grundke-iqbal i. mechanism of neurofibrillary degeneration and pharmacologic therapeutic approach. j neural transm suppl. 2000;59:213-22. review.

93. cheng ly, wang jz, gong cx, pei jj, zaidi t, grundke-iqbal i, iqbal k. multiple forms of phosphatase from human brain: isolation and partial characterization of affi-gel blue binding phosphatases. neurochem res. 2000 jan;25(1):107-20.

94. wang jz, wu q, smith a, grundke-iqbal i, iqbal k. tau is phosphorylated by gsk-3 at several sites found in alzheimer disease and its biological activity markedly inhibited only after it is prephosphorylated by a-kinase. febs lett.1998 sep 25;436(1):28-34.

95. iqbal k, alonso ac, gong cx, khatoon s, pei jj, wang jz, grundke-iqbal i. mechanisms of neurofibrillary degeneration and the formation of neurofibrillary tangles. j neural transm suppl. 1998;53:169-80. review.

96. wang jz, grundke-iqbal i, iqbal k. glycosylation of microtubule-associated protein tau: an abnormal posttranslational modification in alzheimer's disease. nat med. 1996 aug;2(8):871-5.

97. wang jz, grundke-iqbal i, iqbal k. restoration of biological activity ofalzheimer abnormally phosphorylated tau by dephosphorylation with protein phosphatase-2a, -2b and -1. brain res mol brain res. 1996 jun;38(2):200-8.

98. singh tj, wang jz, novak m, kontzekova e, grundke-iqbal i, iqbal k. calcium/calmodulin-dependent protein kinase ii phosphorylates tau at ser-262 but only partially inhibits its binding to microtubules. febs lett. 1996 jun 3;387(2-3):145-8.

99. wang jz, gong cx, zaidi t, grundke-iqbal i, iqbal k. dephosphorylation of alzheimer paired helical filaments by protein phosphatase-2a and -2b. j biol chem. 1995 mar 3;270(9):4854-60.

100. gong cx, shaikh s,wang jz, zaidi t, grundke-iqbal i, iqbal k. phosphatase activity toward abnormally phosphorylated tau: decrease in alzheimer disease brain. j neurochem. 1995 aug;65(2):732-8.

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