Anti-neuroinflammatory agents for the treatment of Alzheimer's disease

Future Medicinal Chemistry

Volumn 5, Issue 13, 2013, Pages 1559-1571

  Zhou, Wei ^a   Hu, Wenhui ^a,b  

^a GUANGZHOU INSTITUTES OF BIOMEDICINE AND HEALTH   (China)

^b GUANGZHOU MEDICAL UNIVERSITY   (China)

Author keywords

[No Author keywords available]

Indexed keywords

4 (4 FLUOROPHENYL) 2 (4 NITROPHENYL) 5 (4 PYRIDYL)IMIDAZOLE; ADVANCED GLYCATION END PRODUCT RECEPTOR; ATORVASTATIN; BAPINEUZUMAB; DICLOFENAC; FPS ZM1; FPS2; IMMUNOGLOBULIN ENHANCER BINDING PROTEIN; INDOMETACIN; INTERLEUKIN 15; INTERLEUKIN 1BETA; INTERLEUKIN 6; MITOGEN ACTIVATED PROTEIN KINASE P38; MONOCYTE CHEMOTACTIC PROTEIN 1; NAPROXEN; PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR GAMMA; PF 4494700; PIOGLITAZONE; PREDNISONE; REACTIVE OXYGEN METABOLITE; ROFECOXIB; ROSIGLITAZONE; SEMAGACESTAT; SOLANEZUMAB; SYNAPTOPHYSIN; TETRANDRINE; TRANSCRIPTION FACTOR AP 1; TRANSFORMING GROWTH FACTOR BETA; TUMOR NECROSIS FACTOR ALPHA; UNCLASSIFIED DRUG; UNINDEXED DRUG;

ALZHEIMER DISEASE; APOPTOSIS; BLOOD BRAIN BARRIER; BRAIN ISCHEMIA; CELL ACTIVATION; CELL DIFFERENTIATION; CELL SURVIVAL; CELL VIABILITY; CYTOKINE PRODUCTION; DRUG DEVELOPMENT; ENCEPHALITIS; FOLLOW UP; GENE EXPRESSION; HUMAN; IC 50; IMMUNE RESPONSE; IMMUNOREACTIVITY; IN VITRO STUDY; IN VIVO STUDY; INTRACELLULAR SIGNALING; MITOSIS; NEUROFIBRILLARY TANGLE; OXIDATIVE STRESS; PHASE 1 CLINICAL TRIAL (TOPIC); PHASE 2 CLINICAL TRIAL (TOPIC); PHASE 3 CLINICAL TRIAL (TOPIC); PRIORITY JOURNAL; PROTEIN PHOSPHORYLATION; REVIEW; SIGNAL TRANSDUCTION; SPATIAL MEMORY; STRUCTURE ACTIVITY RELATION;

ALZHEIMER DISEASE; ANIMALS; ANTI-INFLAMMATORY AGENTS; BRAIN; HUMANS; NF-KAPPA B; P38 MITOGEN-ACTIVATED PROTEIN KINASES; PPAR GAMMA; PYRIDAZINES; RECEPTORS, IMMUNOLOGIC; SIGNAL TRANSDUCTION;

EID: 84884333071     PISSN: 17568919     EISSN: 17568927     Source Type: Journal    
DOI: 10.4155/fmc.13.125     Document Type: Review

References (107)

1. Huang Y, Mucke L. Alzheimer mechanisms and therapeutic strategies. Cell 148(6), 1204-1222 (.2012
2. Wino A, Prince M. World Alzheimer Report 2010: The Global Economic Impact of Dementia. Alzheimer's Disease International, IL, USA, 1-56 (.2010
3. Mangialasche F, Solomon A, Winblad B et al. Alzheimer's disease: Clinical trials and drug development. Lancet Neurol. 9(7), 702-716 (.2010
4. Krause DL, Muller N. Neuroinflammation, microglia and implications for anti-inflammatory treatment in Alzheimer's disease. J. Alzheimer's Dis. 2010, 732806 (.2010
5. Glass CK, Saijo K, Winner B et al. Mechanisms underlying inflammation in neurodegeneration. Cell 140(6), 918-934 (.2010
6. Hirsch EC, Hunot S, Hartmann A. Neuroinflammatory processes in Parkinson's disease. Parkinsonism Relat. Disord. 11(Suppl 1), S9-S15 (.2005
7. McGeer EG, McGeer PL. Inflammatory processes in Alzheimer's disease. Prog. Neuropsychopharmacol. Bio. Psychiatry, 27(5), 741-749 (.2003
8. Spencer JP, Vafeiadou K, Williams RJ, Vauzour D. Neuroinflammation: Modulation by flavonoids and mechanisms of action. Mol. Aspects Med. 33(1), 83-97 (.2012
9. Hensley K. Neuroinflammation in Alzheimer's disease: Mechanisms, pathologic consequences, and potential for therapeutic manipulation. J. Alzheimer's Dis. 21(1), 1-14 (.2010
10. Rogers J, Lubernarod J, Styren SD et al. Expression of immune system-associated antigens by cells of the human central nervous-system- relationship to the pathology of Alzheimers disease. Neurobiol. Aging 9(4), 339-349 (.1988
11. McGeer PL, McGeer EG. Anti-inflammatory drugs in the fight against Alzheimer's disease. Ann. N.Y. Acad. Sci. 777, 213-220 (.1996
12. Rogers J, Kirby LC, Hempelman SR et al. Clinical trial of indomethacin in Alzheimer's disease. Neurology 43(8), 1609-1611 (.1993
13. McGeer PL, Schulzer M, McGeer EG. Arthritis and anti-inflammatory agents as possible protective factors for Alzheimer's disease: A review of 17 epidemiologic studies. Neurology 47(2), 425-432 (.1996
14. Scharf S, Mander A, Ugoni A et al. A double-blind, placebo-controlled trial of diclofenac misoprostol in Alzheimer's disease. Neurology 53(1), 197-201 (.1999
15. Aisen PS, Davis KL, Berg JD et al. A randomized controlled trial of prednisone in Alzheimer's disease. Neurology 54(3), 588-593 (.2000
16. Hoozemans JJM, O'Banion MK. The role of COX-1 and COX-2 in Alzheimer's disease pathology and the therapeutic potentials of non-steroidal anti-inflammatory drugs. Curr. Drug Targets: CNS Neurol. Disord., 4(3), 307-315 (.2005
17. Wyss-Coray T. Inflammation in Alzheimer disease: Driving force, bystander or beneficial response? Nat. Med. 12(9), 1005-1015 (.2006
18. Meda L, Cassatella MA, Szendrei GI et al Activation of microglial cells by b-amyloid protein and interferon g. Nature 374(6523), 647-650 (.1995
19. Yan SD, Chen X, Fu J et al. RAGE and amyloid-b peptide neurotoxicity in Alzheimer's disease. Nature 382(6593), 685-691 (.1996
20. Zilka N, Kazmerova Z, Jadhav S et al. Who fans the flames of Alzheimer's disease brains? Misfolded tau on the crossroad of neurodegenerative and inflammatory pathways. J. Neuroinflammation 9, 47 (.2012
21. Kierdorf K, Erny D, Goldmann T et al. Microglia emerge from erythromyeloid precursors via Pu.1- and Irf8-dependent pathways. Nat. Neurosci. 16(3), 273-280 (.2013
22. Lee CYD, Landreth GE. The role of microglia in amyloid clearance from the AD brain. J. Neural Transm. 117(8), 949-960 (.2010
23. Persson M, Brantefjord M, Hansson E, Ronnback L. Lipopolysaccharide increases microglial GLT-1 expression and glutamate uptake capacity in vitro by a mechanism dependent on TNF-a. Glia 51(2), 111-120 (.2005
24. Kim SU, de Vellis J. Microglia in health and disease. J. Neurosci. Res. 81(3), 302-313 (.2005
25. Hanisch UK, Kettenmann H. Microglia: Active sensor and versatile effector cells in the normal and pathologic brain. Nat. Neurosci. 10(11), 1387-1394 (.2007
26. Mccoy MK, Tansey MG. TNF signaling inhibition in the CNS: Implications for normal brain function and neurodegenerative disease. J. Neuroinflammation 5, 45 (.2008
27. Saijo K, Winner B, Carson CT et al. A Nurr1/CoREST pathway in microglia and astrocytes protects dopaminergic neurons from inflammation-induced death. Cell 137(1), 47-59 (.2009
28. Simi A, Tsakiri N, Wang P et al. Interleukin-1 and inflammatory neurodegeneration. Biochem. Soc. Trans. 35, 1122-1126 (.2007
29. Broussard GJ, Mytar J, Li RC et al. The role of inflammatory processes in Alzheimer's disease. Inflammopharmacology 20(3), 109-126 (.2012
30. Hu W, Ralay Ranaivo H, Craft JM et al. Validation of the neuroinflammation cycle as a drug discovery target using integrative chemical biology and lead compound development with an Alzheimer's disease-related mouse model. Curr. Alzheimer Res. 2(2), 197-205 (.2005
31. Gospodarska E, Kupniewska-Kozak A, Goch G et al. Binding studies of truncated variants of the A b peptide to the V-domain of the RAGE receptor reveal Ab residues responsible for binding. Biochim. Biophys. Acta 1814(5), 592-609 (.2011
32. Brett J, Schmidt AM, Yan SD et al. Survey of the distribution of a newly characterized receptor for advanced glycation end products in tissues. Am. J. Pathol. 143(6), 1699-1712 (.1993
33. Arancio O, Zhang HP, Chen X et al. RAGE potentiates Ab-induced perturbation of neuronal function in transgenic mice. EMBO J. 23(20), 4096-4105 (.2004
34. Deane R, Du Yan S, Submamaryan RK et al. RAGE mediates amyloid b peptide transport across the blood-brain barrier and accumulation in brain. Nat. Med. 9(7), 907-913 (.2003
35. Takuma K, Fang F, Zhang WS et al. RAGE-mediated signaling contributes to intraneuronal transport of amyloid-b and neuronal dysfunction. Proc. Natl. Acad. Sci. USA 106(47), 20021-20026 (.2009
36. Guglielmotto M, Aragno M, Tamagno E et al. AGEs/RAGE complex upregulates BACE1 via NF-kB pathway activation. Neurobiol. Aging 33(1), 196.e113-127 (.2012
37. Cho HJ, Son SM, Jin SM et al. RAGE regulates BACE1 and Ab generation via NFAT1 activation in Alzheimer's disease animal model. FASEB J. 23(8), 2639-2649 (.2009
38. Geroldi D, Falcone C, Emanuele E. Soluble receptor for advanced glycation end products: From disease marker to potential therapeutic target. Curr. Med. Chem. 13(17), 1971-1978 (.2006
39. Webster SJ, Mruthinti S, Hill WD, Buccafusco JJ, Terry AV Jr. An aqueous orally active vaccine targeted against a RAGE/Ab complex as a novel therapeutic for Alzheimer's disease. NeuroMolecular Med. 14(2), 119-130 (.2012
40. Sabbagh MN, Agro A, Bell J, Aisen PS, Schweizer E, Galasko D. PF-04494700, an oral inhibitor of receptor for advanced glycation end products (.RAGE), in Alzheimer disease. Alzheimer Dis. Assoc. Disord. 25(3), 206-212 (.2011
41. Perrone L, Sbai O, Nawroth PP, Bierhaus A. The complexity of sporadic Alzheimer's disease pathogenesis: The role of RAGE as therapeutic target to promote neuroprotection by inhibiting neurovascular dysfunction. Int. J. Alzheimer's Dis. 2012, 734956 (.2012
42. Deane R, Singh I, Sagare AP et al. A multimodal RAGE-specific inhibitor reduces amyloid b-mediated brain disorder in a mouse model of Alzheimer disease. J. Clin. Invest. 122(4), 1377-1392 (.2012
43. Han YT, Choi GI, Son D et al. Ligand-based design, synthesis, and biological evaluation of 2-aminopyrimidines, a novel series of receptor for advanced glycation end products (.RAGE) inhibitors. J. Med. Chem. 55(21), 9120-9135 (.2012
44. Lee YS, Kim H, Kim YH, Roh EJ, Han H, Shin KJ. Synthesis and structure-activity relationships of tri-substituted thiazoles as RAGE antagonists for the treatment of Alzheimer's disease. Bioorg. Med. Chem. Lett. 22(24), 7555-7561 (.2012
45. Hensley K, Floyd RA, Zheng NY et al. p38 kinase is activated in the Alzheimer's disease brain. J. Neurochem. 72(5), 2053-2058 (.1999
46. Sun AY, Liu M, Nguyen XV, Bing GY. p38 MAP kinase is activated at early stages in Alzheimer's disease brain. Exp Neurol. 183(2), 394-405 (.2003
47. Zhu XW, Rottkamp CA, Hartzler A et al. Activation of MKK6, an upstream activator of p38, in Alzheimer's disease. J. Neurochem. 79(2), 311-318 (.2001
48. Kim SH, Smith CJ, Van Eldik LJ. Importance of MAPK pathways for microglial pro-inflammatory cytokine IL-1b production. Neurobiol. Aging 25(4), 431-439 (.2004
49. Xing B, Xin T, Hunter RL, Bing GY. Pioglitazone inhibition of lipopolysaccharide-induced nitric oxide synthase is associated with altered activity of p38 MAP kinase and PI3K/Akt. J. Neuroinflammation 5, 4 (.2008
50. McDonald DR, Bamberger ME, Combs CK, Landreth GE. b amyloid fibrils activate parallel mitogen-activated protein kinase pathways in microglia and THP1 monocytes. J. Neurosci. 18(12), 4451-4460 (.1998
51. Hua LWL, Zhao ML, Cosenza M et al. Role of mitogen-activated protein kinases in inducible nitric oxide synthase and TNF-a expression in human fetal astrocytes. J. Neuroimmunol. 126(1-2), 180-189 (.2002
52. Xie Z, Smith CJ, Van Eldik LJ. Activated glia induce neuron death via NLAP kinase signaling pathways involving JNK and p38. Glia, 45(2), 170-179 (.2004
53. Munoz R, Arias Y, Ferreras JM et al Targeting a marker of the tumour neovasculature using a novel anti-human CD105-immunotoxin containing the non-toxic type 2 ribosome-inactivating protein nigrin b. Cancer Lett. 256(1), 73-80 (.2007
54. Kumar S, Boehm J, Lee JC. p38 MAP kinases: Key signalling molecules as therapeutic targets for inflammatory diseases. Nat. Rev. Drug Discov. 2(9), 717-726 (.2003
55. Underwood DC, Osborn RR, Kotzer CJ et al. SB 239063, a potent p38 MAP kinase inhibitor, reduces inflammatory cytokine production, airways eosinophil infiltration, and persistence. J. Pharmacol. Exp. Ther. 293(1), 281-288 (.2000
56. Yasuda S, Sugiura H, Tanaka H, Takigami S, Yamagata K. p38 MAP kinase inhibitors as potential therapeutic drugs for neural diseases. Cent. Nerv. Syst. Agents Med. Chem. 11(1), 45-59 (.2011
57. Bachstetter AD, Xing B, de Almeida L, Dimayuga ER, Watterson DM, Van Eldik LJ. Microglial p38 a MAPK is a key regulator of proinflammatory cytokine up-regulation induced by toll-like receptor (.TLR) ligands or b-amyloid (.Ab). J. Neuroinflammation 8 (.2011
58. Munoz L, Ranaivo HR, Roy SM et al. Novel p38a MAPK inhibitor suppresses brain proinflammatory cytokine up-regulation and attenuates synaptic dysfunction and behavioral deficits in an Alzheimer's disease mouse model. J. Neuroinflammation 4, 21 (.2007
59. Leister KP, Huang R, Goodwin BL, Chen A, Austin CP, Xia M. Two high throughput screen assays for measurement of TNF-a in THP-1 cells. Curr. Chem. Genomics 5, 21-29 (.2011
60. Ashabi G, Alamdary SZ, Ramin M, Khodagholi F. Reduction of hippocampal apoptosis by intracerebroventricular administration of extracellular signal-regulated protein kinase and/or p38 inhibitors in amyloid b rat model of Alzheimer's disease: Involvement of nuclear-related factor-2 and nuclear factor-kB. Basic Clin. Pharmacol. Toxicol. 112(3), 145-155 (.2013
61. Chang KH, de Pablo Y, Lee HP, Lee HG, Smith MA, Shah K. Cdk5 is a major regulator of p38 cascade: Relevance to neurotoxicity in Alzheimer's disease. J. Neurochem. 113(5), 1221-1229 (.2010
62. Sokolova A, Hill MD, Rahimi F, Warden LA, Halliday GM, Shepherd CE. Monocyte chemoattractant protein-1 plays a dominant role in the chronic inflammation observed in Alzheimer's disease. Brain Pathol. 19(3), 392-398 (.2009
63. Xuan AG, Long DH, Li JH et al. Hydrogen sulfide attenuates spatial memory impairment and hippocampal neuroinflammation in b amyloid rat model of Alzheimer's disease. J. Neuroinflammation 9, 202 (.2012
64. Hou DR, Tian Y, Zhou J, Chen K, Wan S. Butylphthalide improves learning and memory abilities of rats with Alzheimer's disease possibly by inhibiting P38 mitogen-activated protein kinase and enhancing extra-cellular signal regulated kinase expressions. Nanfang Yike Daxue Xuebao 29(8), 1592-1595 (.2009
65. Yamamoto Y, Gaynor RB. Therapeutic potential of inhibition of the NF-kB pathway in the treatment of inflammation and cancer. J. Clin. Invest. 107(2), 135-142 (.2001
66. Granic I, Dolga AM, Nijholt IM, van Dijk G, Eisel ULM. Inflammation and NF-kB in Alzheimer's disease and diabetes. J. Alzheimers Dis. 16(4), 809-821 (.2009
67. Tilstra JS, Clauson CL, Niedernhofer LJ, Robbins PD. NF-kB in aging and disease. Aging Dis. 2(6), 449-465 (.2011
68. He FQ, Qiu BY, Zhang XH et al. Tetrandrine attenuates spatial memory impairment and hippocampal neuroinflammation via inhibiting NF-kB activation in a rat model of Alzheimer's disease induced by amyloid-b(1-42). Brain Res. 1384, 89-96 (.2011
69. Lin ST, Wang Y, Xue Y, Feng DC, Xu Y, Xu LY. Tetrandrine suppresses LPS-induced astrocyte activation via modulating IKKs-I kBa-NF-kB signaling pathway. Mol. Cell Biochem. 315(1-2), 41-49 (.2008
70. Wu SJ, Ng LT. Tetrandrine inhibits proinflammatory cytokines, iNOS and COX- 2 expression in human monocytic cells. Biol. Pharm. Bull. 30(1), 59-62 (.2007
71. Ray B, Lahiri DK. Neuroinflammation in Alzheimer's disease: Different molecular targets and potential therapeutic agents including curcumin. Curr. Opin. Pharmacol. 9(4), 434-444 (.2009
72. Singh S, Aggarwal BB. Activation of transcription factor NF-kB is suppressed by curcumin (.diferuloylmethane). J. Biol. Chem. 270(50), 30235-30235 (.1995
73. Tran TA, McCoy MK, Sporn MB, Tansey MG. The synthetic triterpenoid CDDO-methyl ester modulates microglial activities, inhibits TNF production, and provides dopaminergic neuroprotection. J. Neuroinflammation 5, 14 (.2008
74. Wang C, Li JA, Liu QA et al. Hydrogen-rich saline reduces oxidative stress and inflammation by inhibit of JNK and NF-kB activation in a rat model of amyloid-b-induced Alzheimer's disease. Neurosci. Lett. 491(2), 127-132 (.2011
75. Lee YJ, Choi DY, Lee YK et al. 4-O-methylhonokiol prevents memory impairment in the Tg2576 transgenic mice model of Alzheimer's disease via regulation of b secretase activity. J. Alzheimers Dis. 29(3), 677-690 (.2012
76. Lee YJ, Choi DY, Choi IS et al. Inhibitory effect of 4-O-methylhonokiol on lipopolysaccharide-induced neuroinflammation, amyloidogenesis and memory impairment via inhibition of nuclear factor-kB in vitro and in vivo models. J. Neuroinflammtion 9, 35 (.2012
77. Landreth GE, Heneka MT. Anti-inflammatory actions of peroxisome proliferator-activated receptor g agonists in Alzheimer's disease. Neurobiol. Aging 22(6), 937-944 (.2001
78. Kielian T, Drew PD. Effects of peroxisome proliferator-activated receptor g agonists on central nervous system inflammation. J. Neurosci. Res. 71(3), 315-325 (.2003
79. Sastre M, Dewachter I, Landreth GE et al. Nonsteroidal anti-inflammatory drugs and peroxisome proliferator-activated receptor-g agonists modulate immunostimulated processing of amyloid precursor protein through regulation of b secretase. J. Neurosci. 23(30), 9796-9804 (.2003
80. Bales KR, Verina T, Cummins DJ et al. Apolipoprotein E is essential for amyloid deposition in the APP(V717F) transgenic mouse model of Alzheimer's disease. Proc. Natl Acad. Sci. USA 96(26), 15233-15238 (.1999
81. Ricote M, Li AC, Willson TM, Kelly CJ, Glass CK. The peroxisome proliferator-activated receptor g is a negative regulator of macrophage activation. Nature 391(6662), 79-82 (.1998
82. Bernardo A, Minghetti L. PPAR-g a agonists as regulators of microglial activation and brain inflammation. Curr. Pharm. Design, 12(1), 93-109 (.2006
83. Chung SW, Kang BY, Kim SH et al. Oxidized low density lipoprotein inhibits interleukin-12 production in lipopolysaccharide-activated mouse macrophages via direct interactions between peroxisome proliferator-activated receptor-g and nuclear factor-kB. J. Biol. Chem. 275(42), 32681-32687 (.2000
84. Delerive P, De Bosscher K, Besnard S et al. Peroxisome proliferator-activated receptor a negatively regulates the vascula inflammatory gene response by negative cross-talk with transcription factors NF-kB and AP-1. J. Biol. Chem. 274(45), 32048-32054 (.1999
85. Combs CK, Johnson DE, Karlo JC, Cannady SB, Landreth GE. Inflammatory mechanisms in Alzheimer's disease: Inhibition of b-amyloid-stimulated proinflammatory responses and neurotoxicity by PPAR-g agonists. J Neurosci. 20(2), 558-567 (.2000
86. Mandrekar-Colucci S, Landreth GE. Nuclear receptors as therapeutic targets for Alzheimer's disease. Expert Opin. Ther. Targets 15(9), 1085-1097 (.2011
87. Risner ME, Saunders AM, Altman JFB et al. Efficacy of rosiglitazone in a genetically defined population with mild-to-moderate Alzheimer's disease. Pharmacogenomics J. 6(4), 246-254 (.2006
88. Miller BW, Willett KC, Desilets AR. Rosiglitazone and pioglitazone for the treatment of Alzheimer's disease. Ann. Pharmacother. 45(11), 1416-1424 (.2011
89. Grip O, Janciauskiene S, Lindgren S. Atorvastatin activates PPAR-g and attenuates the inflammatory response in human monocytes. Inflamm. Res. 51(2), 58-62 (.2002
90. Chang CZ, Wu SC, Lin CL, Hwang SL, Howng SL, Kwan AL. Atorvastatin preconditioning attenuates the production of endothelin-1 and prevents experimental vasospasm in rats. Acta Neurochir. 152(8), 1399-1406 (.2010
91. Henn A, Lund S, Hedtjarn M, Schrattenholz A, Porzgen P, Leist M. The suitability of BV2 cells as alternative model system for primary microglia cultures or for animal experiments examining brain inflammation. Altex 26(2), 83-94 (.2009
92. Mirzoeva S, Sawkar A, Zasadzki M et al. Discovery of a 3-amino-6-phenyl-pyridazine derivative as a new synthetic anti-neuroinflammatory compound. J. Med. Chem. 45(3), 563-566 (.2002
93. Craft JM, Watterson DM, Frautschy SA, Van Eldik LJ. Aminopyridazines inhibit b-amyloid-induced glial activation and neuronal damage in vivo. Neurobiol. Aging 25(10), 1283-1292 (.2004
94. Craft JM, Van Eldik LJ, Zasadzki M, Hu WH, Watterson DM. Aminopyridazines attenuate hippocampus-dependent behavioral deficits induced by human b-amyloid in a murine model of neuroinflammation. J. Mol. Neurosci. 24(1), 115-122 (.2004
95. Hu W, Ralay Ranaivo H, Roy SM et al. Development of a novel therapeutic suppressor of brain proinflammatory cytokine up-regulation that attenuates synaptic dysfunction and behavioral deficits. Bioorg. Med. Chem. Lett. 17(2), 414-418 (.2007
96. Zhou W, Zhong GF, Rao XR et al. Identification of aminopyridazine-derived anti-neuroinflammatory agents effective in an Alzheimer's mouse model. ACS Med. Chem. Lett. 3(11), 903-907 (.2012
97. Tweedie D, Ferguson RA, Fishman K et al. Tumor necrosis factor a synthesis inhibitor 3,6́-dithiothalidomide attenuates markers of inflammation, Alzheimer pathology and behavioral deficits in animal models of neuroinflammation and Alzheimer's disease. J. Neuroinflammation 9, 106 (.2012
98. Russo I, Caracciolo L, Tweedie D et al. 3,6́-dithiothalidomide, a new TNF-a synthesis inhibitor, attenuates the effect of Ab (.1-42) intracerebroventricular injection on hippocampal neurogenesis and memory deficit. J. Neurochem. 122(6), 1181-1192 (.2012
99. Gabbita SP, Srivastava MK, Eslami P et al. Early intervention with a small molecule inhibitor for tumor necrosis factor a prevents cognitive deficits in a triple transgenic mouse model of Alzheimer's disease. J. Neuroinflammation 9, 99 (.2012
100. Chavant F, Deguil J, Pain S et al. Imipramine, in part through tumor necrosis factor a inhibition, prevents cognitive decline and b-amyloid accumulation in a mouse model of Alzheimer's disease. J. Pharmacol. Exp. Ther. 332(2), 505-514 (.2010
101. O'Hare E, Scopes DIC, Treherne JM et al. Novel anti-inflammatory compound SEN1176 alleviates behavioral deficits induced following bilateral intrahippocampal injection of aggregated amyloid-b(1-42). J. Alzheimers Dis. 25(2), 219-229 (.2011
102. Hashioka S, McLarnon JG, Ryu JK et al. Pyrazole compound 2-MBAPA as a novel inhibitor of microglial activation and neurotoxicity in vitro and in vivo. J. Alzheimers Dis. 27(3), 531-541 (.2011
103. Zhao H, Wang SL, Qian L et al. Diammonium glycyrrhizinate attenuates Ab (.1-42)-induced neuroinflammation and regulates MAPK and NF-kB pathways in vitro and in vivo. CNS Neurosci. Ther. 19(2), 117-124 (.2013
104. Lee YJ, Choi DY, Yun YP, Han SB, Oh KW, Hong JT. Epigallocatechin-3- gallate prevents systemic inflammation-induced memory deficiency and amyloidogenesis via its anti-neuroinflammatory properties. J. Nutr. Biochem. 24(1), 298-310 (.2013
105. Yuan SM, Gao K, Wang DM et al. Evodiamine improves congnitive abilities in SAMP8 and APP(swe)/PS1(Delta E9) transgenic mouse models of Alzheimer's disease. Acta Pharmacol. Sin. 32(3), 295-302 (.2011
106. Kuang X, Du JR, Chen YS, Wang J, Wang YN. Protective effect of Z-ligustilide against amyloid b-induced neurotoxicity is associated with decreased pro-inflammatory markers in rat brains. Pharmacol., Biochem. Behav. 92(4), 635-641 (.2009
107. Underwood DC, Osborn RR, Bochnowicz S et al. SB 239063, a p38 MAPK inhibitor, reduces neutrophilia, inflammatory cytokines, MMP-9, and fibrosis in lung. Am. J. Physiol. Lung Cell. Mol. Physiol. 279(5), L895-L902 (.2000