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Attenuation of β-amyloid-induced neuroinflammation by KHG21834 in vivo

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Beta-Amyloid (Aβ)-induced neuroinflammation is one of the key events in the development of neurodegenerative disease. We previously reported that KHG21834, a benzothiazole derivative,attenuates Aβ-induced degeneration of cortical and mesencephalic neurons in vitro. In the present work, we show that KHG21834 reduces Aβ-mediated neuroinflammation in brain. In vivo intracerebroventricular infusion of KHG21834leads to decreases in the numbers of activated astrocytes and microglia and level of proinflammatory cytokines such as interleukin-1β and tumor necrosis factor-α induced by Aβ in the hippocampus. This suppression of neuroinflammation is associated with decreased neuron loss, restoration of synaptic dysfunction biomarkers in the hippocampus to control level, and diminished amyloid deposition. These results may suggest the potential therapeutic efficacy of KHG21834 for the treatment of Aβ-mediated neuroinflammation.

Abstract

Beta-Amyloid (Aβ)-induced neuroinflammation is one of the key events in the development of neurodegenerative disease. We previously reported that KHG21834, a benzothiazole derivative,attenuates Aβ-induced degeneration of cortical and mesencephalic neurons in vitro. In the present work, we show that KHG21834 reduces Aβ-mediated neuroinflammation in brain. In vivo intracerebroventricular infusion of KHG21834leads to decreases in the numbers of activated astrocytes and microglia and level of proinflammatory cytokines such as interleukin-1β and tumor necrosis factor-α induced by Aβ in the hippocampus. This suppression of neuroinflammation is associated with decreased neuron loss, restoration of synaptic dysfunction biomarkers in the hippocampus to control level, and diminished amyloid deposition. These results may suggest the potential therapeutic efficacy of KHG21834 for the treatment of Aβ-mediated neuroinflammation.

참고문헌 (41)

  1. Breitner, J. C., "The role of anti-inflammatory drugs in the prevention and treatment of Alzheimer's disease", Annu. Rev. Med., 47, pp.401~411 (1996)
  2. Eikelenboom, P., "Neuroinflammatory perspectives on the two faces of Alzheimer's disease", J. Neural. Transm., 111, pp.281~294 (2004)
  3. Raine, C. S., "Multiple sclerosis: immune system molecule expression in the central nervous system", J. Neuropathol. Exp. Neurol., 53, pp.328~337 (1994)
  4. Matyszak, M. K., "Inflammation in the CNS: balance between immunological privilege and immune responses", Prog. Neurobiol., 56, pp.19~35 (1998)
  5. Giulian, D., "Microglia and the immune pathology of Alzheimer disease", Am. J. Hum. Genet., 65, pp.13~18 (1999)
  6. Gonzalez-Scarano, F., "Microglia as mediators of infammatory and degenerative diseases", Annu. Rev. Neurosci., 22, pp.219~240 (1999)
  7. Qin, L., "Microglia enhance β-amyloid peptide- induced toxicity in cortical and mesencephalic neurons by producing reactive oxygen species", J. Neurochem., 83, pp.973~983 (2002)
  8. Combs, C. K., "β-amyloid stimulation of microglia and monocytes results in TNFα-dependent expression of inducible nitric oxide synthase and neuronal apoptosis", J. Neurosci., 21, pp.1179~1188 (2001)
  9. Gao, H. M., "Microglial activation-mediated delayed and progressive degeneration of rat nigral dopaminergic neurons: relevance to Parkinson's disease", J. Neurochem., 81, pp.1285~1297 (2002)
  10. Liu, Y., "Inhibition by Naloxone stereoisomers of β-amyloid peptide (1-42) induced superoxide production in microglia and degeneration of cortical and mesencephalic neurons", J. Pharmacol. Exp. Ther., 302, pp.1212~1219 (2002)
  11. Knethen, A., "NO-evoked macrophage apoptosis is attenuated by cAMP-induced gene expression", Mol. Med., 5, pp.672~684 (1999)
  12. Heneka, M. T., "Induction of nitric oxide synthase and nitric oxide-mediated apoptosis in neuronal PC12 cells after stimulation with tumor necrosis factor-alpha", lipopolysaccharide, 1998, pp.71, 88~94
  13. Korhonen, R., "Nitric oxide production and signalling in inflammation", Curr. Drug Targets Inflamm. Allergy, 4, pp.471~479 (2005)
  14. Kleinert, H., "Regulation of the expression of inducible nitric oxide synthase", Biol. Chem., 384, pp.1343~1364 (2003)
  15. Bhat, N. R., "Extracellular signal-regulated kinase and p38 subgroups of mitogen-activated protein kinases regulate inducible nitric oxide synthase and tumor necrosis factor-α gene expression in endotoxin-stimulated primary glial cultures", J. Neurosci., 18, pp.1633~1641 (1998)
  16. Ajizian, S. J., "Specific inhibitors of p38 and extracellular signal-regulated kinase mitogen-activated protein kinase pathways block inducible nitric oxide synthase and tumor necrosis factor accumulation in murine macrophages stimulated with lipopolysaccharide and interferon-gamma", J. Infect. Dis., 179, pp.939~944 (1999)
  17. Carter, A. B., "Both Erk and p38 Kinases are necessary for cytokine gene transcription", Am. J. Respir. Cell. Mol. Biol., 20, pp.751~758 (1999)
  18. Moore, A. H., "Neuroinflammation and anti-inflammatory therapy for Alzheimer’s disease", Adv. Drug Deliv. Rev., 54, pp.1627~1656 (2002)
  19. Wang, M. J., "Silymarin protects dopaminergic neurons against lipopolysaccharide-induced neurotoxicity by inhibiting microglia activation", Eur. J. Neurosci., 16, pp.2103~2112 (2002)
  20. Allan, S. M., "Interleukin-1β and neuronal injury", Nat. Rev. Immunol., 5, pp.629~640 (2005)
  21. Emsley, H. C. A., "A randomised phase II study of interleukin-1 receptor antagonist in acute stroke patients", J. Neurol. Neurosurg. Psychiatry, 76, pp.1366~1372 (2005)
  22. Heiser, V., "Identification of benzothiazoles as potential polyglutamine aggregation inhibitors of Huntington's disease by using an automated filter retardation assay", Proc. Natl. Acad. Sci. U.S.A., 통권 : 99, pp.16400~16406 (2002)
  23. Ishiyama, T., "Riluzole slows the progression of neuromuscular dysfunction in the wobbler mouse motor neuron disease", Brain Res., 1019, pp.226~236 (2004)
  24. Mortimer, C. G., "Antitumor Benzothiazoles. 26.1 2-(3,4-Dimethoxyphenyl)-5-fluorobenzothiazole (GW 610, NSC 721648), a simple fluorinated 2-arylbenzothiazole, shows potent and selective inhibitory activity against lung, colon, and breast cancer cell lines", J. Med. Chem., 49, pp.179~185 (2006)
  25. Pietrancosta, N., "Imino-tetrahydro-benzothiazole derivatives as p53 inhibitors: discovery of a highly potent in vivo inhibitor and its action mechanism", J. Med. Chem., 49, pp.3645~3652 (2006)
  26. Mathis, C. A., "A lipophilic thioflavin-T derivative for positron emission tomography (PET) imaging of amyloid in brain", Bioorg. Med. Chem. Lett., 12, pp.295~298 (2002)
  27. Klunk, W. E., "The binding of 2-(4'-methylaminophenyl) benzothiazole to postmortem brain homogenates is dominated by the amyloid component", J. Neurosci., 23, pp.2086~2092 (2003)
  28. Choi, M. M., "Protective effect of benzothiazole derivative KHG21834 on amyloid beta-induced neurotoxicity in PC12 cells and cortical and mesencephalic neurons", Toxicology, 239, pp.156~166 (2007)
  29. Kim, E. A., "Suppression of lipopolysaccharide-induced microglial activation by a benzothiazole derivative" (2010), Mol. Cells (in press)
  30. Small, D. H., "Alzheimer's disease and Aβ toxicity: from top to bottom", Nat. Rev. Neurosci., 2, pp.595~598 (2001)
  31. Sebastiani, G., "The cAMP-specific phosphodiesterase 4B mediates Aβ-induced microglial activation", Neurobiol. Aging, 27, pp.691~701 (2006)
  32. White, J. A., "Differential effects of oligomeric and fibrillar amyloid-beta1-42 on astrocyte-mediated inflammation", Neurobiol. Dis., 18, pp.459~465 (2005)
  33. Craft, J. M., "Aminopyridazines attenuate hippocampus-dependent behavioral deficits induced by human β-amyloid in a murine model of neuroinflammation", J. Mol. Neurosci., 24, pp.115~122 (2004)
  34. Craft. J. M., "Aminopyridazines inhibit β-amyloid-induced glial activation and neuronal damage in vivo", Neurobiol. Aging, 25, pp.1283~1292 (2004)
  35. Craft, J. M., "Interleukin 1 receptor antagonist knockout mice show enhanced microglial activation and neuronal damage induced by intracerebroventricular infusion of human β-amyloid", J. Neuroinflammation, 2, pp.15~23 (2005)
  36. Craft, J. M., "Enhanced susceptibility of S100B transgenic mice to neuroinflammation and neuronal dysfunction induced by intracerebroventricular infusion of human β-amyloid", Glia, 51, pp.209~216 (2005)
  37. Akiyama, H., "Inflammation and Alzheimer's disease", Neurobiol. Aging, 21, pp.383~421 (2000)
  38. Ranaivo, H. R., "Glia as a therapeutic target: selective suppression of human amyloid-β-induced upregulation of brain proinflammatory cytokine production attenuates neurodegeneration", J. Neurosci., 26, pp.662~670 (2006)
  39. Cheramy, A., "Riluzole inhibits release of glutamate in the caudate nucleus of the cat in vitro", Neurosci. Lett., 147, pp.209~212 (1992)
  40. Frautschy, S. A., "Rodent models of Alzheimer’s disease: rat Aβ infusion approaches to amyloid deposits", Neurobiol. Aging, 17, pp.311~321 (1996)
  41. Laursen, S. E., "Intracerebroventricular injections in mice. Some methodological refinements", J. Pharmacol. Methods, 16, pp.355~357 (1986)

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