Treatment with a C5aR antagonist decreases pathology and enhances behavioral performance in murine models of Alzheimer's disease

Journal of Immunology

Volumn 183, Issue 2, 2009, Pages 1375-1383

  Fonseca, Maria I ^a   Ager, Rahasson R ^a   Chu, Shu Hui ^a   Yazan, Ozkan ^a   Sanderson, Sam D ^b   LaFerla, Frank M ^c   Taylor, Stephen M ^d   Woodruff, Trent M ^d   Tenner, Andrea J ^a,c  

^a UNIVERSITY OF CALIFORNIA   (United States)

^b UNIVERSITY OF NEBRASKA AT OMAHA   (United States)

^c UNIVERSITY OF CALIFORNIA   (United States)

^d UNIVERSITY OF QUEENSLAND   (Australia)

Author keywords

[No Author keywords available]

Indexed keywords

AMYLOID; COMPLEMENT COMPONENT C5A RECEPTOR; CYCLIC HEXAPEPTIDE HYDROCINNAMATE (ORNITHINE PROLINE D CYCLOHEXYLALANINE TRYPTOPHAN ARGININE); RECEPTOR BLOCKING AGENT; TAU PROTEIN; UNCLASSIFIED DRUG; COMPLEMENT RECEPTOR; CYCLOPEPTIDE; HYDROCINNAMATE CYCLO(ORNITHYL PROLYL CYCLOHEXYLALANYL TRYPTOPHYL ARGINYL); HYDROCINNAMATE-CYCLO(ORNITHYL-PROLYL-CYCLOHEXYLALANYL-TRYPTOPHYL-ARGINYL);

ALZHEIMER DISEASE; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; BEHAVIOR; CONTROLLED STUDY; FEMALE; GLIA; MALE; MOUSE; NERVE DEGENERATION; NONHUMAN; PASSIVE AVOIDANCE; PATHOLOGY; PRIORITY JOURNAL; PROTEIN PHOSPHORYLATION; ANIMAL; DISEASE MODEL; DRUG ANTAGONISM; DRUG EFFECT; INFLAMMATION; NEUROFIBRILLARY TANGLE; PATHOPHYSIOLOGY; PERSONALITY DISORDER; SENILE PLAQUE;

ALZHEIMER DISEASE; ANIMALS; DISEASE MODELS, ANIMAL; INFLAMMATION; MICE; NERVE DEGENERATION; NEUROFIBRILLARY TANGLES; NEUROGLIA; PEPTIDES, CYCLIC; PERSONALITY DISORDERS; RECEPTOR, ANAPHYLATOXIN C5A; RECEPTORS, COMPLEMENT; SENILE PLAQUES;

EID: 69249152289     PISSN: 00221767     EISSN: 15506606     Source Type: Journal    
DOI: 10.4049/jimmunol.0901005     Document Type: Article

References (72)

1. Terry, R. D., E. Masliah, and L. A. Hansen. 1999. The neuropathology of Alzheimer disease and the structural basis of its cognitive alteration. In Alzheimer Disease, 2nd Ed. R. D. Terry, R. Katzman, K. L. Bick, and S. S. Sisodia, eds. Lippincott Williams & Wilkins, New York, pp. 187-206.
2. Trojanowski, J. Q., and V. M. Lee. 2005. Pathological tau: a loss of normal function or a gain in toxicity? Nat. Neurosci. 8: 1136-1137.
3. Gandy, S. 2005. The role of cerebral amyloid β accumulation in common forms of Alzheimer disease. J. Clin. Invest. 115: 1121-1129.
4. Wyss-Coray, T. 2006. Inflammation in Alzheimer disease: driving force, bystander or beneficial response? Nat. Med. 12: 1005-1015.
5. Shaftel, S. S., W. S. Griffin, and M. K. O'Banion. 2008. The role of interleukin-1 in neuroinflammation and Alzheimer disease: an evolving perspective. J. Neuroinflammation. 5: 7.
6. Aizenstein, H. J., R. D. Nebes, J. A. Saxton, J. C. Price, C. A. Mathis, N. D. Tsopelas, S. K. Ziolko, J. A. James, B. E. Snitz, P. R. Houck, et al. 2008. Frequent amyloid deposition without significant cognitive impairment among the elderly. Arch. Neurol. 65: 1509-1517.
7. Walport, M. J. 2001. Complement: second of two parts. N. Engl. J. Med. 344: 1140-1144.
8. Monk, P. N., A. M. Scola, P. Madala, and D. P. Fairlie. 2007. Function, structure and therapeutic potential of complement C5a receptors. Br. J. Pharmacol. 152: 429-448.
9. Bonifati, D. M., and U. Kishore. 2007. Role of complement in neurodegeneration and neuroinflammation. Mol. Immunol. 44: 999-1010.
10. Rogers, J., N. R. Cooper, S. Webster, J. Schultz, P. L. McGeer, S. D. Styren, W. H. Civin, L. Brachova, B. Bradt, P. Ward, and I. Lieberburg. 1992. Complement activation by β-amyloid in Alzheimer disease. Proc. Natl. Acad. Sci. USA 89: 10016-10020.
11. Bradt, B. M., W. P. Kolb, and N. R. Cooper. 1998. Complement-dependent proinflammatory properties of the Alzheimer's disease β-peptide. J. Exp. Med. 188: 431-438.
12. Akiyama, H., S. Barger, S. Barnum, B. Bradt, J. Bauer, G. M. Cole, N. R. Cooper, P. Eikelenboom, M. Emmerling, B. L. Fiebich, et al. 2000. Inflammation and Alzheimer's disease. Neurobiol. Aging 21: 383-421.
13. Loeffler, D. A., D. M. Camp, and D. A. Bennett. 2008. Plaque complement activation and cognitive loss in Alzheimer's disease. J. Neuroinflammation 5: 9.
14. Zanjani, H., C. E. Finch, C. Kemper, J. Atkinson, D. McKeel, J. C. Morris, and J. L. Price. 2005. Complement activation in very early Alzheimer disease. Alzheimer Dis. Assoc. Disord. 19: 55-66.
15. Webster, S., L. F. Lue, L. Brachova, A. J. Tenner, P. L. McGeer, K. Terai, D. G. Walker, B. Bradt, N. R. Cooper, and J. Rogers. 1997. Molecular and cellular characterization of the membrane attack complex, C5b-9, in Alzheimer's disease. Neurobiol. Aging 18: 415-421.
16. Shen, Y., L. Lue, L. Yang, A. Roher, Y. Kuo, R. Strohmeyer, W. J. Goux, V. Lee, G. V. Johnson, S. D. Webster, et al. 2001. Complement activation by neurofibrillary tangles in Alzheimer's disease. Neurosci. Lett. 305: 165-168.
17. Meyer-Luehmann, M., T. L. Spires-Jones, C. Prada, M. Garcia-Alloza, A. de Calignon, A. Rozkalne, J. Koenigsknecht-Talboo, D. M. Holtzman, B. J. Bacskai, and B. T. Hyman. 2008. Rapid appearance and local toxicity of amyloid-β plaques in a mouse model of Alzheimer's disease. Nature 451: 720-724.
18. Busche, M. A., G. Eichhoff, H. Adelsberger, D. Abramowski, K. H. Wiederhold, C. Haass, M. Staufenbiel, A. Konnerth, and O. Garaschuk. 2008. Clusters of hyperactive neurons near amyloid plaques in a mouse model of Alzheimer's disease. Science 321: 1686-1689.
19. Fonseca, M. I., J. Zhou, M. Botto, and A. J. Tenner. 2004. Absence of C1q leads to less neuropathology in transgenic mouse models of Alzheimer's disease. J. Neurosci. 24: 6457-6465.
20. Fan, R., K. DeFilippis, and W. E. Van Nostrand. 2007. Induction of complement proteins in a mouse model for cerebral microvascular A β deposition. J. Neuroinflammation 4: 22.
21. Zhou, J., M. I. Fonseca, K. Pisalyaput, and A. J. Tenner. 2008. Complement C3 and C4 expression in C1q sufficient and deficient mouse models of Alzheimer's disease. J. Neurochem. 106: 2080-2092.
22. Maier, M., Y. Peng, L. Jiang, T. J. Seabrook, M. C. Carroll, and C. A. Lemere. 2008. Complement C3 deficiency leads to accelerated amyloid β plaque deposition and neurodegeneration and modulation of the microglia/macrophage phenotype in amyloid precursor protein transgenic mice. J. Neurosci. 28: 6333-6341.
23. Pisalyaput, K., and A. J. Tenner. 2008. Complement component C1q inhibits β-amyloid- and serum amyloid P-induced neurotoxicity via caspase- and calpainin-dependent mechanisms. J. Neurochem. 104: 696-707.
24. Stevens, B., N. J. Allen, L. E. Vazquez, G. R. Howell, K. S. Christopherson, N. Nouri, K. D. Micheva, A. K. Mehalow, A. D. Huberman, B. Stafford, et al. 2007. The classical complement cascade mediates CNS synapse elimination. Cell 131: 1164-1178.
25. Woodruff, T. M., S. Pollitt, L. M. Proctor, S. Z. Stocks, H. D. Manthey, H. M. Williams, I. B. Mahadevan, I. A. Shiels, and S. M. Taylor. 2005. Increased potency of a novel complement factor 5a receptor antagonist in a rat model of inflammatory bowel disease. J. Pharmacol. Exp. Ther. 314: 811-817.
26. Woodruff, T. M., J. W. Crane, L. M. Proctor, K. M. Buller, A. B. Shek, K. de Vos, S. Pollitt, H. M. Williams, I. A. Shiels, P. N. Monk, and S. M. Taylor. 2006. Therapeutic activity of C5a receptor antagonists in a rat model of neurodegeneration. FASEB. J. 20: 1407-1417.
27. Woodruff, T. M., K. J. Costantini, J. W. Crane, J. D. Atkin, P. N. Monk, S. M. Taylor, and P. G. Noakes. 2008. The complement factor C5a contributes to pathology in a rat model of amyotrophic lateral sclerosis. J. Immunol. 181: 8727-8734.
28. Sewell, D. L., B. Nacewicz, F. Liu, S. Macvilay, A. Erdei, J. D. Lambris, M. Sandor, and Z. Fabry. 2004. Complement C3 and C5 play critical roles in traumatic brain cryoinjury: blocking effects on neutrophil extravasation by C5a receptor antagonist. J. Neuroimmunol. 155: 55-63.
29. Hsiao, K. K., P. Chapman, S. Nilsen, C. Eckman, Y. Harigaya, S. Younkin, F. Yang, and G. Cole. 1996. Correlative memory deficits, Aβ elevations, and amyloid plaques in transgenic mice. Science 274: 99-102.
30. Oddo, S., A. Caccamo, J. D. Shepherd, M. P. Murphy, T. E. Golde, R. Kayed, R. Metherate, M. P. Mattson, Y. Akbari, and F. M. LaFerla. 2003. Triple-transgenic model of Alzheimer's disease with plaques and tangles: intracellular Aβ and synaptic dysfunction. Neuron 39: 409-421.
31. Reid, R. C., G. Abbenante, S. M. Taylor, and D. P. Fairlie. 2003. A convergent solution-phase synthesis of the macrocycle Ac-Phe-[Orn-Pro-D-Cha-Trp- Arg], a potent new antiinflammatory drug. J. Org. Chem. 68: 4464-4471.
32. Necula, M., R. Kayed, S. Milton, and C. G. Glabe. 2007. Small molecule inhibitors of aggregation indicate that amyloid β oligomerization and fibrillization pathways are independent and distinct. J. Biol. Chem. 282: 10311-10324.
33. Hirata-Fukae, C., H. F. Li, H. S. Hoe, A. J. Gray, S. S. Minami, K. Hamada, T. Niikura, F. Hua, H. Tsukagoshi-Nagai, Y. Horikoshi-Sakuraba, et al. 2008. Females exhibit more extensive amyloid, but not tau, pathology in an Alzheimer transgenic model. Brain Res. 1216: 92-103.
34. Decker, M. W., T. M. Gill, and J. L. McGaugh. 1990. Concurrent muscarinic and β-adrenergic blockade in rats impairs place-learning in a water maze and retention of inhibitory avoidance. Brain Res. 513: 81-85.
35. King, D. L., and G. W. Arendash. 2002. Behavioral characterization of the Tg2576 transgenic model of Alzheimer's disease through 19 months. Physiol. Behav. 75: 627-642.
36. Nolte, C., T. Möller, T. Walter, and H. Kettenmann. 1996. Complement 5a controls motility of murine microglial cells in vitro via activation of an inhibitory G-protein and the rearrangement of the actin cytoskeleton. Neuroscience 73: 1091-1107.
37. Tenner, A. J., and K. Pisalyaput. 2008. The complement system in the CNS: thinking again. In Central Nervous System Diseases and Inflammation. T. E. Lane, M. J. Carson, C. Bergmann, and T. Wyss-Coray, eds. Springer, New York, pp. 153-174.
38. Afagh, A., B. J. Cummings, D. H. Cribbs, C. W. Cotman, and A. J. Tenner. 1996. Localization and cell association of C1q in Alzheimer's disease brain. Exp. Neurol. 138: 22-32.
39. Yao, J., L. Harvath, D. L. Gilbert, and C. A. Colton. 1990. Chemotaxis by a CNS macrophage, the microglia. J. Neurosci. Res. 27: 36-42.
40. Alexander, J. J., A. J. Anderson, S. R. Barnum, B. Stevens, and A. J. Tenner. 2008. The complement cascade: Yin-Yang in neuroinflammation: neuro-protection and -degeneration. J. Neurochem. 107: 1169-1187.
41. Rojo, L. E., J. A. Fernandez, A. A. Maccioni, J. M. Jimenez, and R. B. Maccioni. 2008. Neuroinflammation: implications for the pathogenesis and molecular diagnosis of Alzheimer's disease. Arch. Med. Res. 39: 1-16.
42. Flaherty, P., M. L. Radhakrishnan, T. Dinh, R. A. Rebres, T. I. Roach, M. I. Jordan, and A. P. Arkin. 2008. A dual receptor crosstalk model of G-protein-coupled signal transduction. PLoS. Comput. Biol. 4: e1000185.
43. Zhang, X., Y. Kimura, C. Fang, L. Zhou, G. Sfyroera, J. D. Lambris, R. A. Wetsel, T. Miwa, and W. C. Song. 2007. Regulation of Toll-like receptor-mediated inflammatory response by complement in vivo. Blood 110: 228-236.
44. Hawlisch, H., Y. Belkaid, R. Baelder, D. Hildeman, C. Gerard, and J. Kohl. 2005. C5a negatively regulates Toll-like receptor 4-induced immune responses. Immunity 22: 415-426. (Pubitemid 40545108)
45. Patel, S. N., J. Berghout, F. E. Lovegrove, K. Ayi, A. Conroy, L. Serghides, G. Min-oo, D. C. Gowda, J. V. Sarma, D. Rittirsch, et al. 2008. C5 deficiency and C5a or C5aR blockade protects against cerebral malaria. J. Exp. Med. 205: 1133-1143.
46. Tahara, K., H. D. Kim, J. J. Jin, J. A. Maxwell, L. Li, and K. Fukuchi. 2006. Role of Toll-like receptor signalling in Aβ uptake and clearance. Brain 129: 3006-3019.
47. Jana, M., C. A. Palencia, and K. Pahan. 2008. Fibrillar amyloid-β peptides activate microglia via TLR2: implications for Alzheimer's disease. J. Immunol. 181: 7254-7262.
48. Lim, G. P., F. Yang, T. Chu, P. Chen, W. Beech, B. Teter, T. Tran, O. Ubeda, K. H. Ashe, S. A. Frautschy, and G. M. Cole. 2000. Ibuprofen suppresses plaque pathology and inflammation in a mouse model for Alzheimer's disease. J. Neurosci. 20: 5709-5714.
49. Ryman, D., Y. Gao, and B. T. Lamb. 2008. Genetic loci modulating amyloid-β levels in a mouse model of Alzheimer's disease. Neurobiol. Aging 29: 1190-1198.
50. Jain, N. K., C. S. Patil, S. K. Kulkarni, and A. Singh. 2002. Modulatory role of cyclooxygenase inhibitors in aging- and scopolamine or lipopolysaccharide-induced cognitive dysfunction in mice. Behav. Brain Res. 133: 369-376.
51. Ognibene, E., S. Middei, S. Daniele, W. Adriani, O. Ghirardi, A. Caprioli, and G. Laviola. 2005. Aspects of spatial memory and behavioral disinhibition in Tg2576 transgenic mice as a model of Alzheimer's disease. Behav. Brain Res. 156: 225-232.
52. Bergamaschini, L., E. Rossi, C. Storini, S. Pizzimenti, M. Distaso, C. Perego, A. De Luigi, C. Vergani, and D. S. Grazia. 2004. Peripheral treatment with enoxaparin, a low molecular weight heparin, reduces plaques and β-amyloid accumulation in a mouse model of Alzheimer's disease. J. Neurosci. 24: 4181-4186.
53. Wyss-Coray, T., F. Yan, A. H. Lin, J. D. Lambris, J. J. Alexander, R. J. Quigg, and E. Masliah. 2002. Prominent neurodegeneration and increased plaque formation in complement-inhibited Alzheimer's mice. Proc. Natl. Acad. Sci. USA 99: 10837-10842.
54. Pasinetti, G. M., G. Tocco, S. Sakhi, W. D. Musleh, M. G. DeSimoni, P. Mascarucci, S. Schreiber, M. Baudry, and C. E. Finch. 1996. Hereditary deficiencies in complement C5 are associated with intensified neurodegenerative responses that implicate new roles for the C-system in neuronal and astrocytic functions. Neurobiol. Dis. 3: 197-204.
55. Rahpeymai, Y., M. A. Hietala, U. Wilhelmsson, A. Fotheringham, I. Davies, A. K. Nilsson, J. Zwirner, R. A. Wetsel, C. Gerard, M. Pekny, and M. Pekna. 2006. Complement: a novel factor in basal and ischemia-induced neurogenesis. EMBO. J. 25: 1364-1374.
56. Rus, H., C. Cudrici, and F. Niculescu. 2005. C5b-9 complement complex in autoimmune demyelination and multiple sclerosis: dual role in neuroinflammation and neuroprotection. Ann. Med. 37: 97-104.
57. Jauneau, A. C., A. Ischenko, A. Chatagner, M. Benard, P. Chan, M. T. Schouft, C. Patte, H. Vaudry, and M. Fontaine. 2006. Interleukin 1b and anaphylatoxins exert a synergistic effect on NGF expression by astrocytes. J. Neuroinflammation 3: 8.
58. Heese, K., C. Hock, and U. Otten. 1998. Inflammatory signals induce neurotrophin expression in human microglial cells. J. Neurochem. 70: 699-707. (Pubitemid 28079359)
59. Kang, H. J., L. Bao, Y. Xu, R. J. Quigg, P. C. Giclas, and V. M. Holers. 2004. Increased serum C3 levels in Crry transgenic mice partially abrogates its complement inhibitory effects. Clin. Exp. Immunol. 136: 194-199.
60. Markiewski, M. M., R. A. DeAngelis, F. Benencia, S. K. Ricklin-Lichtsteiner, A. Koutoulaki, C. Gerard, G. Coukos, and J. D. Lambris. 2008. Modulation of the antitumor immune response by complement. Nat. Immunol. 9: 1225-1235.
61. Nataf, S., P. F. Stahel, N. Davoust, and S. R. Barnum. 1999. Complement anaphylatoxin receptors on neurons: new tricks for old receptors? Trends Neurosci. 22: 397-402.
62. Otto, M., H. Hawlisch, P. N. Monk, M. Muller, A. Klos, C. L. Karp, and J. Kohl. 2004. C5a mutants are potent antagonists of the C5a receptor (CD88) and of C5L2: position 69 is the locus that determines agonism or antagonism. J. Biol. Chem. 279: 142-151.
63. Gavrilyuk, V., S. Kalinin, B. S. Hilbush, A. Middlecamp, S. McGuire, D. Pelligrino, G. Weinberg, and D. L. Feinstein. 2005. Identification of complement 5a-like receptor (C5L2) from astrocytes: characterization of antiinflammatory properties. J. Neurochem. 92: 1140-1149.
64. Rittirsch, D., M. A. Flierl, B. A. Nadeau, D. E. Day, M. Huber-Lang, C. R. Mackay, F. S. Zetoune, N. P. Gerard, K. Cianflone, J. Kohl, et al. 2008. Functional roles for C5a receptors in sepsis. Nat. Med. 14: 551-557.
65. Schnatbaum, K., E. Locardi, D. Scharn, U. Richter, H. Hawlisch, J. Knolle, and T. Polakowski. 2006. Peptidomimetic C5a receptor antagonists with hydrophobic substitutions at the C-terminus: increased receptor specificity and in vivo activity. Bioorg. Med. Chem. Lett. 16: 5088-5092.
66. Morgan, B. P., M. Griffiths, H. Khanom, S. M. Taylor, and J. W. Neal. 2004. Blockade of the C5a receptor fails to protect against experimental autoimmune encephalomyelitis in rats. Clin. Exp. Immunol. 138: 430-438.
67. Frautschy, S. A., F. S. Yang, M. Irrizarry, B. Hyman, T. C. Saido, K. Hsiao, and G. M. Cole. 1998. Microglial response to amyloid plaques in APPsw transgenic mice. Am. J. Pathol. 152: 307-317.
68. Bogestal, Y. R., S. R. Barnum, P. L. Smith, V. Mattisson, M. Pekny, and M. Pekna. 2007. Signaling through C5aR is not involved in basal neurogenesis. J. Neurosci. Res. 85: 2892-2897.
69. Rother, R. P., S. A. Rollins, C. F. Mojcik, R. A. Brodsky, and L. Bell. 2007. Discovery and development of the complement inhibitor eculizumab for the treatment of paroxysmal nocturnal hemoglobinuria. Nat. Biotech. 25: 1256-1264.
70. Hepburn, N. J., A. S. Williams, M. A. Nunn, J. C. Chamberlain-Banoub, J. Hamer, B. P. Morgan, and C. L. Harris. 2007. In vivo characterization and therapeutic efficacy of a C5-specific inhibitor from the soft tick Ornithodoros moubata. J. Biol. Chem. 282: 8292-8299.
71. Woodruff, T. M., L. M. Proctor, A. J. Strachan, and S. M. Taylor. 2006. Complement factor 5a as a therapeutic target. Drugs Future 31: 325-334.
72. Kohl, J. 2006. Drug evaluation: the C5a receptor antagonist PMX-53. Curr. Opin. Mol. Ther. 8: 529-538. (Pubitemid 44921809)