Advances Achievements of Traditional Chinese Medicine on the Signaling Pathways in Central Nervous Degenerative Diseases

doi:10.3969/j.issn.2095-1396.2017.03.005

Abstract

Abstract: It is found that Chinese medicine play a important role in the prevention and treatment of the central nervous system diseases（AD，PD，cerebral ischemia，etc） by adjusting the key signaling molecule such as Wnt，β-catenin，TCF/LEF，PI3K，AKT，mTOR，NF-κB，Cyt-C，Bcl-2 family，Caspases enzyme，etc，along with in-depth study of the pathogenesis on Chinese medicine used to delay aging and prevent age-related diseases. This article focuses on three signaling pathways （Wnt/β-catenin，PI3K/Akt，mitochondrial apoptosis） and reviews the prevention and treatment of Chinese medicine on the central nervous system degenerative diseases mainly.

Key words: Wnt/&beta, -catenin signaling pathway, mitochondrial apoptosis, PI3K/Akt signaling pathway, Alzheimer&rsquo, s disease（ AD）, Parkinson&rsquo, s disease（ PD）

CLC Number:

R285，R964

ZHANG Li-na，ZHANG Xin，XUE Juan，ZHANG Dan-shen. Advances Achievements of Traditional Chinese Medicine on the Signaling Pathways in Central Nervous Degenerative Diseases[J]. Acta Neuropharmacologica, 2017, 7(3): 33-42.

References

1. Hanife Guler Tanir, Sayeste Demirezen, Mehmet Sinan Beksaç. Relation of the Wnt/β-catenin signaling pathway with gynecological cancers[J].J Turkish Biology, 2010, 34(3): 227-234．

2. Katharina Seitz, Verena Dürsch, Jakub Harnoš, et al. β-Arrestin interacts with the beta/gamma subunits of trimeric G-proteins and dishevelled in the Wnt/Ca2+pathway in xenopus gastrulation[J]. Plos One, 2014, 9(1):1-11.

3. Hans A Kestler, Michael Kühl. From individual Wnt pathways towards a Wnt signalling network[J]. Philosophical Transactions of the Royal Society of London, 2008, 363(1495):1333-1347.

4. Andrey Voronkov, Stefan Krauss. Wnt/beta-catenin signaling and small molecule inhibitors[J]. Current Pharmaceutical Design, 2013, 19(4):634-664.

5. Lu Tao, Liviu Aron, Joseph Zullo, et al. REST and stress resistance in ageing and Alzheimer's disease[J]. Nature, 2014, 507(7493): 448-454.

6. Jayhong A Chong, Jose Tapia-Ramirez, Sandra Kim, et al. REST: A mammalian silencer protein that restricts sodium channel gene expression to neurons[J]. Cell, 1995, 80(6):949-957.

7. Christopher J Schoenherr, David J Anderson. The neuron-restrictive silencer factor (nrsf): a coordinate repressor of multiple neuron-specific genes[J]. Science, 1995, 267(5202):1360-1363.

8. Hu Yuan-yuan, Sun Qian-wen, Zhang Chen, et al. RE1 silencing transcription factor (REST) negatively regulates ALL1-fused from chromosome 1q (AF1q) gene transcription[J]. BMC Molecular Biology, 2015, 16(1):1-8.

9. Jin Nana, Yin Xiao-min, Yu Dian, et al. Truncation and activation of GSK-3β by calpain I: a molecular mechanism links to tau hyperphosphorylation in Alzheimer's disease[J]. Sci Rep, 2015, 5（1）: 1-13

10. Darocha-Souto B, Coma M, Pérez-Nievas B G, et al. Activation of glycogen synthase kinase-3 beta mediates β-amyloid induced neuritic damage in Alzheimer's disease [J]. Neurobiology of Disease, 2012, 45(1):425-437.

11. Masashi Kitazawa, David Cheng, Michelle R Tsukamoto, et al. Blocking interleukin-1 signaling rescues cognition, attenuates tau pathology, and restores neuronal β-catenin pathway function in an Alzheimer's disease model[J]. J Immunology, 2011, 187(12):6539-6549.

12. Dunning Christopher, Mcgauran Gavin, Willén Katarina, et al. Direct high affinity interaction between Aβ42 and GSK3α stimulates hyperphosphorylation of tau. A new molecular link in Alzheimer's disease?[J]. Acs Chemical Neuroscience, 2016, 7(2):161-170.

13. Zhang Ying-hua, Sun Yan, Wang Fei, et al. Downregulating the canonical wnt/β-catenin signaling pathway attenuates the susceptibility to autism-like phenotypes by decreasing oxidative stress[J]. Neurochemical Research, 2012, 37(7):1409-1419.

14. Kyung-Min Noh, Jee-Yeon Hwang, Antonia Follenzi, et al. Repressor element-1 silencing transcription factor (REST)-dependent epigenetic remodeling is critical to ischemia-induced neuronal death[J]. Proceedings of the National Academy of Sciences of the United States of America, 2012, 109(16):E962- E972.

15. Wang Wen-ya, Yang Yi, Ying Chun-yi, et al. Inhibition of glycogen synthase kinase-3beta protects dopaminergic neurons from MPTP toxicity[J]. Neuropharmacology, 2007, 52(8):1678-1684.

16. F L'Episcopo, C Tirolo, N Testa, et al. Reactive astrocytes and Wnt/β-catenin signaling link nigrostriatal injury to repair in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine model of Parkinson's disease[J]. Neurobiology of Disease, 2011, 41(2):508-527.

17. Tang Mian-zhi, J Carlos Villaescusa, Sarah X Luo, et al. Interactions of wnt/β-catenin signaling and sonic hedgehog regulate the neurogenesis of ventral midbrain dopamine neurons[J]. J Neuroscience the Official Journal of the Society for Neuroscience, 2010, 30(27):9280-9291.

18. Juliette D Godin, Ghislaine Poizat, Mirian A Hickey, et al. Mutant huntingtin-impaired degradation of β-catenin causes neurotoxicity in Huntington's disease[J]. Embo J, 2010, 29(14):2433-2445.

19. Pascale Dupont, Marie-Therese Besson, Jerome Devaux, et al. Reducing canonical Wingless/Wnt signaling pathway confers protection against mutant Huntingtin toxicity in Drosophila[J]. Neurobiology of Disease, 2015, 47(2):237-247.

20. Francesca L'Episcopo, Janelle Drouin-Ouellet, Cataldo Tirolo, et al. GSK-3β-induced Tau pathology drives hippocampal neuronal cell death in Huntington's disease: involvement of astrocyte–neuron interactions [J]. Cell Death & Disease, 2016, 7(4):1-14.

21. Hans Clevers, Roel Nusse. Wnt/β-catenin signaling and disease[J]. Cell, 2012, 149(6):1192-1205.

22. Brian H Anderton, Rejith Dayanandan, Richard Killick, et al. Does dysregulation of the Notch and wingless/Wnt pathways underlie the pathogenesis of Alzheimer's disease?[J]. Molecular Medicine Today, 2000, 6(2):54-59.

23. Ernest Arenas. Wnt signaling in midbrain dopaminergic neuron development and regenerative medicine for Parkinson's disease[J]. J Molecular Cell Biology, 2014, 6(1):42-53.

24. Dai Ting-li, Zhang Chan, Peng Fang, et al. Depletion of canonical Wnt signaling components has a neuroprotective effect on midbrain dopaminergic neurons in an MPTP-induced mouse model of Parkinson’s disease[J]. Experimental & Therapeutic Medicine, 2014, 8(2):384-390.

25. Wang Chun-yan, Zheng Wei, Wang Tao, et al. Huperzine A activates Wnt/β-catenin signaling and enhances the nonamyloidogenic pathway in an Alzheimer transgenic mouse model[J]. Neuropsychopharmacology Official Publication of the American College of Neuropsychopharmacology, 2011, 36(5):1073-1089.

26. Zhang Xiong, Yin Wen-ke, Shi Xiao-dong, et al. Curcumin activates Wnt/β-catenin signaling pathway through inhibiting the activity of GSK-3β in APPswe transfected SY5Y cells[J]. European J Pharmaceutical Sciences Official J European Federation for Pharmaceutical Sciences, 2011, 42(5):540-546.

27. Tiwari S K, Agarwal S, Seth B, et al. Curcumin-loaded nanoparticles potently induce adult neurogenesis and reverse cognitive deficits in alzheimer’s disease model via canonical wnt/β-catenin pathway[j]. Acs nano, 2014, 8(1):76-103.

28. Anshuman Sinha, Riyaj S Tamboli, Brashket Seth B, et al. Neuroprotective role of novel triazine derivatives by activating wnt/β catenin signaling pathway in rodent models of Alzheimer’s disease[J]. Molecular Neurobiology, 2015, 52(1):638-652.

29. Yao Ying-jia, Gao Zhong, Liang Wen-bo, et al. Osthole promotes neuronal differentiation and inhibits apoptosis via Wnt/β-catenin signaling in an Alzheimer's disease model[J]. Toxicology & Applied Pharmacology, 2015, 289(3):474-481.

30. Yao Ying, Chen Xian-chun, Bao Yu-ting, et al. Puerarin inhibits β-amyloid peptide 1-42-induced tau hyperphosphorylation via the Wnt/β-catenin signaling pathway[J].Molecular Medicine Reports, 2017,16(6):9081-9085.

31. Giuseppe Esposito, Daniele De Filippis, Rosa Carnuccio, et al. The marijuana component cannabidiol inhibits β-amyloid-induced tau protein hyperphosphorylation through Wnt/β-catenin pathway rescue in PC12 cells[J]. J Molecular Medicine, 2006, 84(3):253-258.

32. Zeng K, Wang X, Hong F U, et al. Inhibition of β-Amyloid Protein (Aβ)-Induced Neurotoxicity by Icariin via Wnt/β-Catenin Signaling Pathway[J]. Chinese Pharmaceutical J, 2011, 59(6):542-550.

33. Yang Sha-sha, Wei Qin, Chen Shi-ya, et al. Effects of cistanche deserticola on behavior and expression of gsk-3β in hippocampus of rat model of Parkinson's disease[J]. Rehabilitation Medicine, 2016, 26(6):24-27.

34. Sun Fang-ling, Wang Wen, Zuo Wei, et al. Promoting neurogenesis via Wnt/β-catenin signaling pathway accounts for the neurorestorative effects of morroniside against cerebral ischemia injury[J]. European J Pharmacology, 2014, 738:214-221.

35. 邓勇, 王键, 谭辉,等. 脑络欣通对气虚血瘀型中脑动脉阻塞再灌注大鼠海马及额顶叶皮质Wnt3a、Wnt5a和β-Catenin表达的影响[J]. 安徽中医药大学学报, 2017, 36(3):59-63.

36. Wen Jing, Wang Jian, Luo Shi-lan, et al. Advances in studies on regulating effects of Wnt/β-catenin signaling pathway on neurovascular unit after cerebral Ischemia and related medicine[J].Chinese Pharmacological Bulletin, 2016,31(9):1713-1724.

37. Park J W, Cheng S Y. Activation of PI3K by thyroid hormone nuclear receptors[M]// S H Domains. Springer International Publishing, 2015: 91-110.

38. Wang Long, Cheng Shan-shan, Yin Zhen-yu, et al. Conditional inactivation of Akt three isoforms causes tau hyperphosphorylation in the brain[J]. Molecular Neurodegeneration, 2015, 10(1):1-7.

39. Robert Eves, Robyn Oldham, Jia Lilly , et al. The roles of akt isoforms in the regulation of podosome formation in fibroblasts and extracellular matrix invasion[J]. Cancers, 2015, 7(1):96-111.

40. Michael D Kaytor, Harry T Orr. The GSK3 beta signaling cascade and neurodegenerative disease[J]. Current Opinion in Neurobiology, 2002, 12(3):275-278.

41. Li Yu-juan, Zeng Min-ting, Chen Wei-qiang, et al. Dexmedetomidine reduces isoflurane-induced neuroapoptosis partly by preserving PI3K/Akt pathway in the hippocampus of neonatal rats[J]. Plos One, 2014, 9(4):1-11.

42. Wang Wei-ping, Shi Zhi-qin, Yu Jiang-hua, et al. Effect of recombinant human erythropoietin on hippocampal p-Akt and caspase-9 expressions in rats with status epilepticus and the mechanism[J]. J Southern Medical University, 2010, 30(1):64-69.

43. Irena Dimov, Desanka Tasi, Ivan Stefanovi, et al. New insights into molecular basis of glioblastoma multiforme and associated immunosuppression[J]. Acta Facultatis Medicae Naissensis, 2013, 30(4):165-184.

44. Hsu Ya-yun, Chen Cheng-sheng, Wu Sheng-nan, et al. Berberine activates Nrf2 nuclear translocation and protects against oxidative damage via a phosphatidylinositol 3-kinase/Akt-dependent mechanism in NSC34 motor neuron-like cells[J]. European J Pharmaceutical Sciences Official J European Federation for Pharmaceutical Sciences, 2012, 46(5):415-425.

45. Fan C L, Jiang J, Liu H C, et al. Forkhead box protein M1 predicts outcome in human osteosarcoma[J]. International J Clinical & Experimental Medicine, 2015, 8(9):15563-15568.

46. Masayuki Fukui, Hye Joung Choi, Bao Ting-zhu. Mechanism for the protective effect of resveratrol against oxidative stress-induced neuronal death[J]. Free Radical Biology & Medicine, 2010, 49(5):800-813.

47. Suzanne Timmons, Meghan Coakley McCarthy, Aileen M Moloney, et al. Akt signal transduction dysfunction in Parkinson's disease[J]. Neuroscience Letters, 2009, 467(1):30-35.

48. Cristina Malagelada, Jin Zong-hao, Lloyd A Greene. RTP801 is induced in Parkinson's disease and mediates neuron death by inhibiting Akt phosphorylation/activation[J]. J Neuroscience the Official J Society for Neuroscience, 2008, 28(53):14363-14371.

49. Tanjala T Gipson, Michael Van Doren Johnston. Plasticity and mTOR: towards restoration of impaired synaptic plasticity in mTOR-related neurogenetic disorders[J]. Neural Plasticity, 2012, 2012(1):486402-486412.

50. Qi Hong-yi, Han Yi-fan, Rong Jian-hui. Potential roles of PI3K/Akt and Nrf2–Keap1 pathways in regulating hormesis of Z-ligustilide in PC12 cells against oxygen and glucose deprivation[J]. Neuropharmacology, 2012, 62(4):1659-1670.

51. Yin Xiao-min, Chen Chen, Xu Ting, et al. Tetrahydroxystilbene glucoside modulates amyloid precursor protein processing via activation of AKT-GSK3β pathway in cells and in APP/PS1 transgenic mice [J]. Biochem Biophys Res Commun, 2017:1-7.

52. Zhang Ling-ling, Huang Lin-hong, Chen Liang-wei, et al. Neuroprotection by tetrahydroxystilbene glucoside in the MPTP mouse model of Parkinson's disease[J]. Toxicology Letters, 2013, 222(2):155-163.

53. Qin Rong, Li Xiao-bing, Li Gang, et al. Protection by tetrahydroxystilbene glucoside against neurotoxicity induced by MPP+: the involvement of PI3K/Akt pathway activation[J]. Toxicology Letters, 2011, 202(1):1-7.

54. Chen Wen-fang, Wu Li, Du Zhong-rui, et al. Neuroprotective properties of icariin in MPTP-induced mouse model of Parkinson's disease: Involvement of PI3K/Akt and MEK/ERK signaling pathways[J]. Phytomedicine, 2016, 25(1):93-99.

55. Zhang Dong, Wang Zhe, Sheng Chen-xia, et al. Icariin prevents amyloid beta-induced apoptosis via the pi3k/akt pathway in pc-12 cells[J]. Evidence-based complementary and alternative medicine : eCAM, 2015, 2015:235265-235274.

56. Dong Hui-min, Mao Shan-ping, Mao Shan-pin, et al. Tanshinone IIA protects PC12 cells from Î²-amyloid(25-35)-induced apoptosis via PI3K/Akt signaling pathway[J]. Molecular Biology Reports, 2012, 39(6):6495-6503.

57. Lu Y, Jin Y, Sui H J, et al. Sarsasapogenin inhibits amyloid beta-protein induced decrease of synaptophysin in hippocampal neurons of neonatal rats via up-regulating PI3K/Akt/GSK3 pathway[J]. Chinese J Pharmacology & Toxicology, 2013, 27(4):635-640.

58. Teng Le-sheng, Meng Qing-fan, Lu Jia-hui, et al. Liquiritin modulates ERK- and AKT/GSK-3β-dependent pathways to protect against glutamate-induced cell damage in differentiated PC12 cells[J]. Molecular Medicine Reports, 2014, 10(2):818-824.

59. Stephanie Bleicken, Gunnar Jeschke, Carolin Stegmueller, et al. Structural model of active Bax at the membrane[J]. Molecular Cell, 2014, 56(4):496-505.

60. Jisen Huai, Lars Jöckel, Karen Schrader, et al. Role of caspases and non-caspase proteases in cell death[J]. F1000 Biology Reports, 2010, 2(1):48-53.

61. 安涛. Caspase在细胞凋亡过程中切割ARF-BP1蛋白的研究[D]. 厦门：厦门大学, 2014.

62. Bao Juan, Yang Qi-dong, Zhou Lin, et al. Study of neuronal apoptosis and changes in expression of the proteins related to the mitochondrial pathway after aβ1–42 injection in the rat hippocampus[J]. Neuroembryology & Aging, 2009, 5(4):156-160.

63. Fatemeh Shaerzadeh, Fereshteh Motamedi, Dariush Minai-Tehrani, et al. Monitoring of neuronal loss in the hippocampus of aβ-injected rat: autophagy, mitophagy, and mitochondrial biogenesis stand against apoptosis[J]. Neuromolecular Medicine, 2014, 16(1):175-190.

64. Fredrik H Sterky, Alexander F Hoffman, Dusanka Milenkovic, et al. Altered dopamine metabolism and increased vulnerability to MPTP in mice with partial deficiency of mitochondrial complex I in dopamine neurons[J]. Human Molecular Genetics, 2012, 21(5):1078-1089.

65. Masakatsu Kanazawa, Hiroyuki Ohba, Shingo Nishiyama, et al. Effects of MPTP on serotonergic neuronal systems and mitochondrial complex i activity in the living brain: a pet study on conscious rhesus monkeys[J]. Journal of Nuclear Medicine, 2017, 58(7):1111-1116.

66. Chen Su-juan, Qian Ren, Zhang Jin-fei, et al. N-acetyl-L-cysteine protects against cadmium-induced neuronal apoptosis by inhibiting ROS-dependent activation of Akt/mTOR pathway in mouse brain[J]. Neuropathology & Applied Neurobiology, 2015, 40(6):759-777.

67. 袁燕. 镉对大鼠大脑皮质神经细胞毒性损伤的机制[D]. 扬州：扬州大学, 2012.

68. Jiang Chen-yang, Yuan Yan, Hu Fei-fei, et al. Cadmium induces pc12 cells apoptosis via an extracellular signal-regulated kinase and c-jun n-terminal kinase-mediated mitochondrial apoptotic pathway[J]. Biological Trace Element Research, 2014, 158(2):249-258.

69. Yang Xiao-ping, Liu Tao-yan, Qin Xiao-yan, et al. Potential protection of 2,3,5,4'-tetrahydroxystilbene-2-O-β-d-glucoside against staurosporine-induced toxicity on cultured rat hippocampus neurons[J]. Neuroscience Letters, 2014, 576(1):79-83.

70. Zhang Ru-yi, Sun Fang-ling, Zhang Lan, et al. Tetrahydroxystilbene glucoside inhibits α-synuclein aggregation and apoptosis in A53T α-synuclein-transfected cells exposed to MPP+[J]. Canadian J Physiologys Pharmacology, 2017, 95(6) :750-758.

71. Sun Fang-ling, Zhang Lan, Zhang Ru-yi, et al. Tetrahydroxystilbene glucoside protects human neuroblastoma SH-SY5Y cells against MPP+-induced cytotoxicity[J]. European J Pharmacology, 2011, 660(2-3):283-290.

72. He Hong, Wang Song-hai, Tian Ji-yu, et al. Protective effects of 2,3,5,4'-tetrahydroxystilbene-2-O-β-D-glucoside in the MPTP-induced mouse model of Parkinson's disease: Involvement of reactive oxygen species-mediated JNK, P38 and mitochondrial pathways[J]. European J Pharmacology, 2015, 767(2):175-182.

73. Zhao Q, Yang X, Cai D, et al. Echinacoside protects against MPP+-induced neuronal apoptosis via ros/atf3/chop pathway regulation[J]. Neurosci Bull, 2016, 32(4):349-362.

74. Zhu M, Lu C, Li W. Transient exposure to echinacoside is sufficient to activate Trk signaling and protect neuronal cells from rotenone[J]. J Neurochemistry, 2013, 124(4):571-580.

75. Geng Xing-chao, Tian Xue-fei, Tu Peng-fei, et al. Neuroprotective effects of echinacoside in the mouse MPTP model of Parkinson's disease[J]. European Journal of Pharmacology, 2007, 564(3):66-74.

76. Wang Hong-quan, Xu Yu-xia, Yan Jie, et al. Acteoside protects human neuroblastoma SH-SY5Y cells against beta-amyloid-induced cell injury[J]. Brain Research, 2009, 1283:139-147.

77. Peng X M, Gao L, Huo S X, et al. The mechanism of memory enhancement of acteoside (verbascoside) in the senescent mouse model induced by a combination of d-gal and alcl3[J]. Phytotherapy Research, 2015, 29(8):1137-1144.

78. Liu Bao-jun, Zhang Hong-ying, Xu Chang-qing, et al. Neuroprotective effects of icariin on corticosterone-induced apoptosis in primary cultured rat hippocampal neurons[J]. Brain Research, 2011, 1375(4):59-67.

79. Xu Ai-li, Jiang Ming-chun, Chen Xiao-han, et al. Icariin protects against MPP+-induced neurotoxicity in MES23.5 cells[J]. Sheng LI Xue Bao, 2016, 68(5):585-591.

80. Hu Sheng-quan, Han Ren-wen, Mak Shing-hung, et al. Protection against 1-methyl-4-phenylpyridinium ion (MPP+)-induced apoptosis by water extract of ginseng (Panax ginseng C.A. Meyer) in SH-SY5Y cells[J]. Journal of Ethnopharmacology, 2011, 135(1):34-42.

81. Wang Ting, Gu Jun, Wu Peng-fei, et al. Protection by tetrahydroxystilbene glucoside against cerebral ischemia: involvement of JNK, SIRT1, and NF-κB pathways and inhibition of intracellular ROS/RNS generation[J]. Free Radical Biology & Medicine, 2009, 47(3):229-240.

[1]	YANG-Lin，AI-Jing. Research Progress of Brain-Derived Estrogen in Alzheimer’s Disease [J]. Acta Neuropharmacologica, 2019, 9(5): 50-64.
[2]	ZHANG Shuai，AI Jing. Glutamate Dysfunction and Alzheimer’s Disease [J]. Acta Neuropharmacologica, 2018, 8(6): 9-20.
[3]	CUI Su-ying, SONG Jin-zhi, CUI Xiang-yu, HU Xiao, DING Hui, YE Hui, ZHANG Yong-he. Intracerebroventricular Streptozocin-induced Alzheimer’s Disease-like Sleep Disorders: Role of the GABAergic System in the Parabrachial Complex [J]. Acta Neuropharmacologica, 2018, 8(5): 96-97.
[4]	YU Li-li1，2，XU Li1，WANG Yi-nuo1，XUE Lu-ning1，Gou Ji-wei1，LI Hong-bo1，HOU Xue-qin1，ZHANG Han-ting1. Effects of Osthole on Learning and Memory and the Estrogen Pathway in Ovariectomized Rats [J]. Acta Neuropharmacologica, 2018, 8(4): 7-8.
[5]	WANG Hao1, ZHANG Fang-fang1, FU Hua-rong1, ZHOU Yan-meng1, LIU Xin1, HOU Xue-qin 1, HU Wei2, Rolf Hansen2, XU Ying3, James O’Donnell3, ZHANG Han-ting1,2. Targeting PDE4 for Alzheimer’s Disease and Alcoholism: An implication in Alcohol-Related Dementia? [J]. Acta Neuropharmacologica, 2018, 8(4): 39-41.
[6]	YANG Wen-zhong1, ZHOU Xue-yan1, MA Tao1,2,3. Impaired mRNA Translational Capacity is Correlated with Aging-Dependent Memory Deficits and Behavioral Inflexibility* [J]. Acta Neuropharmacologica, 2018, 8(4): 50-52.
[7]	WANG Jia-Yue，DUAN Yan-Hong，Wang Xin-He，Zhang Xu-Liang，Xu Mei-Chen, Cao Xiao-Hua . The Effect of PHA-543613 on Memory Disorders in Presenilin1 and Presenilin2 Conditional Double Knockout Mice* [J]. Acta Neuropharmacologica, 2018, 8(4): 52-53.
[8]	LIU Nuo，WANG Zhen-zhen，CHEN Nai-hong. The Role of Gut Flora in the Pathogenesis of Alzheimer’s Disease [J]. Acta Neuropharmacologica, 2017, 7(5): 28-.
[9]	GAO Zhi-hong1，ZUO Ya-qi2，ZHANG Xiao-li1. A New Idea of Astragaloside-Induced Bone Marrow Mesenchymal Stem Cells in the Treatment of Parkinson’s Disease [J]. Acta Neuropharmacologica, 2017, 7(5): 39-44.
[10]	REN Jing，ZHANG Dan-shen. Research Progress of Curcumin in the Treatment of Nervous System Diseases [J]. Acta Neuropharmacologica, 2017, 7(5): 45-51.
[11]	HOU Wen-shu，ZHANG Li. Research Progress on Therapeutic Target of Effective Ingredients of Traditional Chinese Medicine in Treating Alzheimer’s Disease [J]. Acta Neuropharmacologica, 2017, 7(5): 59-64.
[12]	WANG Cui, GUO Tong-lin, SHEN Li-xia. Study on the Neuroprotective Effects of Phytoestrogens in Alzheimer’s Disease [J]. Acta Neuropharmacologica, 2017, 7(4): 43-52.
[13]	BAI Yan-chang，JIA Yan-li，SONG Ya-xue，WANG Jian-hua. Advance of Functional Magnetic Resonance Imaging of Brain in Alzheimer’s Disease [J]. Acta Neuropharmacologica, 2017, 7(3): 6-11.
[14]	DU Guan-tao， LIN Jing-ran,LIU Guang-jun， HONG Hao. Research Progress on the Correlation Between Alzheimer’s Disease and Depression [J]. Acta Neuropharmacologica, 2016, 6(6): 40-44.