A synthetic derivative of the natural product rocaglaol is a potent inhibitor of cytokine-mediated signaling and shows neuroprotective activity in vitro and in animal models of Parkinson's disease and traumatic brain injury

Molecular Pharmacology

Volumn 67, Issue 5, 2005, Pages 1544-1555

  Fahrig, Thomas ^a   Gerlach, I ^a   Horvath E ^a  

^a BAYER PHARMA AG   (Germany)

Author keywords

[No Author keywords available]

Indexed keywords

1 METHYL 4 PHENYLPYRIDINIUM; 1,2,3,6 TETRAHYDRO 1 METHYL 4 PHENYLPYRIDINE; ANTIINFLAMMATORY AGENT; CYCLOOXYGENASE 2; IMMUNOGLOBULIN ENHANCER BINDING PROTEIN; NATURAL PRODUCT; NEUROPROTECTIVE AGENT; NITRIC OXIDE SYNTHASE; ROCAGLAOL; TRANSCRIPTION FACTOR; TRANSCRIPTION FACTOR AP 1; UNCLASSIFIED DRUG;

ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ANTIINFLAMMATORY ACTIVITY; ARTICLE; BRAIN INFARCTION; BRAIN INJURY; CELL CULTURE; CONTROLLED STUDY; DEGENERATIVE DISEASE; DOPAMINERGIC NERVE CELL; DOSE RESPONSE; DRUG MECHANISM; GLIA CELL; IMMUNOBLOTTING; IMMUNOCYTOCHEMISTRY; INFLAMMATION; NERVE DEGENERATION; NONHUMAN; PARKINSON DISEASE; PATHOGENESIS; PRIORITY JOURNAL; RAT; SUBDURAL HEMATOMA; SYNTHESIS;

ANIMALS; BENZOFURANS; BRAIN INJURIES; CELLS, CULTURED; CYTOKINES; DISEASE MODELS, ANIMAL; DOSE-RESPONSE RELATIONSHIP, DRUG; HUMANS; MALE; MICE; MICE, INBRED C57BL; NEUROPROTECTIVE AGENTS; PARKINSON DISEASE; PLANT EXTRACTS; RATS; RATS, WISTAR;

EID: 17844403724     PISSN: 0026895X     EISSN: None     Source Type: Journal    
DOI: 10.1124/mol.104.008177     Document Type: Article

References (40)

1. Allan SM and Rothwell NJ (2001) Cytokines and acute neurodegeneration. Nat Rev Neurosci 2:734-744.
2. Basu A, Krady JK, O'Malley M, Styren SD, DeKosky ST and Levison SW (2002) The type 1 interleukin-1 receptor is essential for the efficient activation of microglia and the induction of multiple proinflammatory mediators in response to brain injury. J Neurosci 22:6071-6082.
3. Baumann B, Bohnenstengel F, Siegmund D, Wajant H, Weber C, Herr I, Debatin K-M, Proksch P, and Wirth T (2002) Rocaglamide derivatives are potent inhibitors of NF-κB activation in T-cells. J Biol Chem 277:44791-44800.
4. Bézard E, Dovero S, Bioulac B, and Gross CE (1997) Kinetics of nigral degeneration in a chronic model of MPTP-treated mice. Neurosci Lett 234:47-50.
5. Cassarino DS, Halvorsen EM, Swerdlow RH, Abramova NN, Parker WD Jr, Sturgill TW, and Bennett JP Jr (2000) Interaction among mitochondria, mitogen-activated protein kinases and nuclear factor-κB in cellular models of Parkinson's disease. J Neurochem 74:1384-1392.
6. Deng L, Wang C, Spencer E, Yang L, Braun A, You J, Slaughter C, Pickart C, and Chen ZJ (2000) Activation of the IkB kinase complex by TRAF6 requires a dimeric ubiquitin-conjugating enzyme complex and a unique polyubiquitin chain. Cell 103:351-361.
7. Eijkenboom M, Gerlach I, Jork R, Lowe D, and van der Staay FJ (2000) Effects of subdural haematoma on sensorimotor functioning and spatial learning in rats. Neuropharmacology 39:817-834.
8. Ferrer I, Blanco R, Carmona M, Puig B, Barrachinaq M, Gómez C, and Ambrosio S (2001) Active, phosphorylation-dependent mitogen-activated protein kinase (MAPK/ERK), stress-activated protein kinase/c-Jun N-terminal kinase (SAPK/JNK) and p38 kinase expression in Parkinson's disease and dementia with Lewy bodies. J Neural Transm 108:1383-1396.
9. Franklin KBJ and Paxinos G (1997) The Mouse Brain in Stereotaxic Coordinates, Academic Press, San Diego.
10. + induces phosphorylated c-Jun in dopaminergic neurons of mesencephalic cultures. Parkinsonism Relat Disord 8:19-22.
11. Hirsch EC (2000) Glial cells and Parkinson's disease. J Neurol 247 (Suppl 2):II58-II62.
12. Hunot S, Brugg B, Ricard D, Michel PP, Muriel M-P, Ruberg M, Faucheux BA, Agid Y, and Hirsch EC (1997) Nuclear translocation of NF-κB is increased in dopaminergic neurons of patients with Parkinson's disease. Proc Natl Acad Sci USA 94:7531-7536.
13. Hoozemans JJM, Veerhuis R, Rozemuller AJM, and Eikelenboom P (2002) The pathological cascade of Alzheimer's disease: the role of inflammation and its therapeutic implications. Drugs Today 38:429-443.
14. Janssens S and Beyaert R (2002) A universal role for MyD88 in TLR/IL-1R-mediated signaling. Trends Biochem Sci 27:474-482.
15. Kaltschmidt B, Uherek M, Volk B, Baeuerle PA, and Kaltschmidt C (1997) Transcription factor NF-κB is activated in primary neurons by amyloid β peptides and in neurons surrounding early plaques from patients with Alzheimer disease. Proc Natl Acad Sci USA 94:2642-2647.
16. Karin M and Lin A (2002) NF-κB at the crossroads of life and death. Nat Immunol 3:221-227.
17. Knott C, Stern G, and Wilkin GP (2000) Inflammatory regulators in Parkinson's disease: iNOS, lipocortin-1 and cyclooxygenases 1 and -2. Mol Cell Neurosci 16:724-739.
18. Kyriakis JM and Avruch J (2001) Mammalian mitogen-activated protein kinase signal transduction pathways activated by stress and inflammation. Physiol Rev 81:807-869.
19. Marks-Konczalik J, Chu SC, and Moss J (1998) Cytokine-mediated transcriptional induction of the human inducible nitric oxide synthase gene requires both activator protein 1 and nuclear factor κB-binding sites. J Biol Chem 273:22201-22208.
20. Medzhitov R (2001) Toll-like receptors and innate immunity. Nat Rev Immunol 1:135-145.
21. Nagatsu T, Mogi M, Ichinose H, and Togari A (2000) Cytokines in Parkinson's disease. J Neural Transm Suppl 58:143-151.
22. Nelson EL, Liang CL, Sinton CM, and German DC (1996) Midbrain dopaminergic neurons in the mouse: computer-assisted mapping. J Comp Neurol 369:361-371.
23. Ping D, Boekhoudt GH, Rogers EM, and Boss JM (1999) Nuclear factor-κB p65 mediates the assembly and activation of the TNF-responsive element of the murine monocyte chemoattractant-1 gene. J Immunol 162:727-734.
24. Pizzi M, Goffi F, Boroni F, Benarese M, Perkins SE, Liou H-C, and Spano P (2002) Opposing roles for NF-κB/Rel factors p65 and c-rel in the modulation of neuron survival elicited by glutamate and interleukin-1β. J Biol Chem 277:20717-20723.
25. Proksch P, Edrada R, Ebel R, Bohnenstengel FI, and Nugroho BW (2001) Chemistry and biological activity of rocaglamide derivatives and related compounds in Aglaia species (Meliaceae). Curr Org Chem 5:923-938.
26. Rahman A, Anwar KN, and Malik AB (2000) Protein kinase C-ζ mediates TNFα-induced ICAM-1 gene transcription in endothelial cells. Am J Physiol 279:C906-C914.
27. Read MA, Whitley MZ, Gupta S, Pierce JW, Best J, Davis RJ, and Collins T (1997) Tumor necrosis factor α-induced E-selectin expression is activated by the nuclear factor-κB and C-JUN N-terminal kinase/p38 mitogen-activated protein kinase pathways. J Biol Chem 272:2753-2761.
28. Roebuck KA (1999) Oxidant stress regulation of IL-8 and ICAM-1 gene expression: differential activation and binding of the transcription factors AP-1 and NF-κB. Int J Mol Med 4:223-230.
29. Schneider A, Martin-Villalba A, Weih F, Vogel J, Wirth T, and Schwaninger M (1999) NF-κB is activated and promotes cell death in focal cerebral ischemia. Nat Med 5:554-559.
30. Shaulian E and Karin M (2002) AP-1 as a regulator of cell life and death. Nat Cell Biol 4:E131-E136.
31. Shi CS and Kehrl JH (2003) Tumor necrosis factor (TNF)-induced germinal center kinase-related (GCKR) and stress-activated protein kinase (SAPK) activation depends upon the E2/E3 complex Ubc13-Uev1A/TNF receptor-associated factor 2 (TRAF2). J Biol Chem 278:15429-15434.
32. Sun L, Deng L, Chee-Kwee E, Zong-Ping X, and Chen ZJ (2004) The TRAF6 ubiquitin ligase and TAK1 kinase mediate IKK activation by BCL10 and MALT1 in T lymphocytes. Mol Cell 14:289-301.
33. Takaesu G, Surabhi RM, Park KJ, Ninomiya-Tsuji J, Matsumoto K, and Gaynor RB (2003) TAK1 is critical for IκB kinase-mediated activation of the NF-κB pathway. J Mol Biol 326:105-115.
34. Tang ED, Wang CY, Xiong Y, and Guan KL (2003) A role for NF-κB essential modifier/IκB kinase γ (NEMO/IKKγ) ubiquitination in the activation of the IκB kinase complex by tumor necrosis factor-α. J Biol Chem 278:37297-37305.
35. Teismann P and Ferger B (2001) Inhibition of the cyclooxygenase isoenzymes COX-1 and COX-2 provide neuroprotection in the MPTP-mouse model of Parkinson's disease. Synapse 39:167-174.
36. Tong L, Toliver-Kinsky T, Rassin D, Werrbach-Perez K, and Perez-Polo JR (2003) Hyperoxia increases AP-1 DNA binding in rat brain. Neurochem Res 28:111-115.
37. Wajant H, Henkler F, and Scheurich P (2001) The TNF-receptor-associated factor family. Scaffold molecules for cytokine receptors, kinases and their regulators. Cell Signalling 13:389-400.
38. Wang C, Deng L, Hong M, Akkaraju GR, Inoue JI, and Zhijian JC (2001) TAK1 is a ubiquitin-dependent kinase of MKK and IKK. Nature (Lond) 412:346-351.
39. Yamamoto K, Arakawa T, Ueda N, and Yamamoto S (1995) Transcriptional roles of nuclear factor κB and nuclear factor-interleukin-6 in tumor necrosis factor α-dependent induction of cyclooxygenase-2 in MC3T3-E1 cells. J Biol Chem 270:31315-31320.
40. Zhu X, Ogawa O, Wang Y, Perry G, and Smith MA (2003) JKK1, an upstream activator of JNK/SAPK, is activated in Alzheimer's disease. J Neurochem 85:87-93.