Search tips
Search criteria 


Logo of molmedLink to Publisher's site
Mol Med. 1999 September; 5(9): 569–582.
PMCID: PMC2230464

Inhibition of complement as a therapeutic approach in inflammatory central nervous system (CNS) disease.

Full text

Full text is available as a scanned copy of the original print version. Get a printable copy (PDF file) of the complete article (2.3M), or click on a page image below to browse page by page. Links to PubMed are also available for Selected References.

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Morgan BP, Gasque P, Singhrao S, Piddlesden SJ. The role of complement in disorders of the nervous system. Immunopharmacology. 1997 Dec;38(1-2):43–50. [PubMed]
  • Yasojima K, Schwab C, McGeer EG, McGeer PL. Up-regulated production and activation of the complement system in Alzheimer's disease brain. Am J Pathol. 1999 Mar;154(3):927–936. [PubMed]
  • Nataf S, Stahel PF, Davoust N, Barnum SR. Complement anaphylatoxin receptors on neurons: new tricks for old receptors? Trends Neurosci. 1999 Sep;22(9):397–402. [PubMed]
  • Liszewski MK, Atkinson JP. Novel complement inhibitors. Expert Opin Investig Drugs. 1998 Mar;7(3):323–331. [PubMed]
  • Morgan BP. Complement regulatory molecules: application to therapy and transplantation. Immunol Today. 1995 Jun;16(6):257–259. [PubMed]
  • Pascual M, French LE. Complement in human diseases: looking towards the 21st century. Immunol Today. 1995 Feb;16(2):58–61. [PubMed]
  • Bühler L, Friedman T, Iacomini J, Cooper DK. Xenotransplantation--state of the art--update 1999. Front Biosci. 1999 Apr 15;4:D416–D432. [PubMed]
  • McGeer PL, McGeer EG. Inflammation of the brain in Alzheimer's disease: implications for therapy. J Leukoc Biol. 1999 Apr;65(4):409–415. [PubMed]
  • Shoulson I. Experimental therapeutics of neurodegenerative disorders: unmet needs. Science. 1998 Nov 6;282(5391):1072–1074. [PubMed]
  • Ernst RL, Hay JW. The US economic and social costs of Alzheimer's disease revisited. Am J Public Health. 1994 Aug;84(8):1261–1264. [PubMed]
  • Scolding NJ, Morgan BP, Compston DA. The expression of complement regulatory proteins by adult human oligodendrocytes. J Neuroimmunol. 1998 Apr 1;84(1):69–75. [PubMed]
  • Stahel PF, Morganti-Kossmann MC, Kossmann T. The role of the complement system in traumatic brain injury. Brain Res Brain Res Rev. 1998 Aug;27(3):243–256. [PubMed]
  • Broadwell RD, Sofroniew MV. Serum proteins bypass the blood-brain fluid barriers for extracellular entry to the central nervous system. Exp Neurol. 1993 Apr;120(2):245–263. [PubMed]
  • Kossmann T, Stahel PF, Morganti-Kossmann MC, Jones JL, Barnum SR. Elevated levels of the complement components C3 and factor B in ventricular cerebrospinal fluid of patients with traumatic brain injury. J Neuroimmunol. 1997 Mar;73(1-2):63–69. [PubMed]
  • Stahel PF, Nadal D, Pfister HW, Paradisis PM, Barnum SR. Complement C3 and factor B cerebrospinal fluid concentrations in bacterial and aseptic meningitis. Lancet. 1997 Jun 28;349(9069):1886–1887. [PubMed]
  • Stahel PF, Frei K, Fontana A, Eugster HP, Ault BH, Barnum SR. Evidence for intrathecal synthesis of alternative pathway complement activation proteins in experimental meningitis. Am J Pathol. 1997 Oct;151(4):897–904. [PubMed]
  • Stahel PF, Frei K, Eugster HP, Fontana A, Hummel KM, Wetsel RA, Ames RS, Barnum SR. TNF-alpha-mediated expression of the receptor for anaphylatoxin C5a on neurons in experimental Listeria meningoencephalitis. J Immunol. 1997 Jul 15;159(2):861–869. [PubMed]
  • Gasque P, Singhrao SK, Neal JW, Wang P, Sayah S, Fontaine M, Morgan BP. The receptor for complement anaphylatoxin C3a is expressed by myeloid cells and nonmyeloid cells in inflamed human central nervous system: analysis in multiple sclerosis and bacterial meningitis. J Immunol. 1998 Apr 1;160(7):3543–3554. [PubMed]
  • Müller-Ladner U, Jones JL, Wetsel RA, Gay S, Raine CS, Barnum SR. Enhanced expression of chemotactic receptors in multiple sclerosis lesions. J Neurol Sci. 1996 Dec;144(1-2):135–141. [PubMed]
  • Gasque P, Singhrao SK, Neal JW, Götze O, Morgan BP. Expression of the receptor for complement C5a (CD88) is up-regulated on reactive astrocytes, microglia, and endothelial cells in the inflamed human central nervous system. Am J Pathol. 1997 Jan;150(1):31–41. [PubMed]
  • Nataf S, Davoust N, Barnum SR. Kinetics of anaphylatoxin C5a receptor expression during experimental allergic encephalomyelitis. J Neuroimmunol. 1998 Nov 2;91(1-2):147–155. [PubMed]
  • Nataf S, Davoust N, Ames RS, Barnum SR. Human T cells express the C5a receptor and are chemoattracted to C5a. J Immunol. 1999 Apr 1;162(7):4018–4023. [PubMed]
  • Davoust N, Jones J, Stahel PF, Ames RS, Barnum SR. Receptor for the C3a anaphylatoxin is expressed by neurons and glial cells. Glia. 1999 May;26(3):201–211. [PubMed]
  • Stahel PF, Kossmann T, Morganti-Kossmann MC, Hans VH, Barnum SR. Experimental diffuse axonal injury induces enhanced neuronal C5a receptor mRNA expression in rats. Brain Res Mol Brain Res. 1997 Oct 15;50(1-2):205–212. [PubMed]
  • Pasinetti GM, Johnson SA, Rozovsky I, Lampert-Etchells M, Morgan DG, Gordon MN, Morgan TE, Willoughby D, Finch CE. Complement C1qB and C4 mRNAs responses to lesioning in rat brain. Exp Neurol. 1992 Nov;118(2):117–125. [PubMed]
  • Campbell IL, Stalder AK, Akwa Y, Pagenstecher A, Asensio VC. Transgenic models to study the actions of cytokines in the central nervous system. Neuroimmunomodulation. 1998 May-Aug;5(3-4):126–135. [PubMed]
  • Barnum SR, Jones JL, Müller-Ladner U, Samimi A, Campbell IL. Chronic complement C3 gene expression in the CNS of transgenic mice with astrocyte-targeted interleukin-6 expression. Glia. 1996 Oct;18(2):107–117. [PubMed]
  • Paradisis PM, Campbell IL, Barnum SR. Elevated complement C5a receptor expression on neurons and glia in astrocyte-targeted interleukin-3 transgenic mice. Glia. 1998 Nov;24(3):338–345. [PubMed]
  • Wetsel RA. Structure, function and cellular expression of complement anaphylatoxin receptors. Curr Opin Immunol. 1995 Feb;7(1):48–53. [PubMed]
  • Czermak BJ, Sarma V, Bless NM, Schmal H, Friedl HP, Ward PA. In vitro and in vivo dependency of chemokine generation on C5a and TNF-alpha. J Immunol. 1999 Feb 15;162(4):2321–2325. [PubMed]
  • Glabinski AR, Ransohoff RM. Chemokines and chemokine receptors in CNS pathology. J Neurovirol. 1999 Feb;5(1):3–12. [PubMed]
  • Martiney JA, Cuff C, Litwak M, Berman J, Brosnan CF. Cytokine-induced inflammation in the central nervous system revisited. Neurochem Res. 1998 Mar;23(3):349–359. [PubMed]
  • McCoy R, Haviland DL, Molmenti EP, Ziambaras T, Wetsel RA, Perlmutter DH. N-formylpeptide and complement C5a receptors are expressed in liver cells and mediate hepatic acute phase gene regulation. J Exp Med. 1995 Jul 1;182(1):207–217. [PMC free article] [PubMed]
  • Czermak BJ, Lentsch AB, Bless NM, Schmal H, Friedl HP, Ward PA. Synergistic enhancement of chemokine generation and lung injury by C5a or the membrane attack complex of complement. Am J Pathol. 1999 May;154(5):1513–1524. [PubMed]
  • Webster S, Lue LF, Brachova L, Tenner AJ, McGeer PL, Terai K, Walker DG, Bradt B, Cooper NR, Rogers J. Molecular and cellular characterization of the membrane attack complex, C5b-9, in Alzheimer's disease. Neurobiol Aging. 1997 Jul-Aug;18(4):415–421. [PubMed]
  • Storch MK, Piddlesden S, Haltia M, Iivanainen M, Morgan P, Lassmann H. Multiple sclerosis: in situ evidence for antibody- and complement-mediated demyelination. Ann Neurol. 1998 Apr;43(4):465–471. [PubMed]
  • Ottonello L, Corcione A, Tortolina G, Airoldi I, Albesiano E, Favre A, D'Agostino R, Malavasi F, Pistoia V, Dallegri F. rC5a directs the in vitro migration of human memory and naive tonsillar B lymphocytes: implications for B cell trafficking in secondary lymphoid tissues. J Immunol. 1999 Jun 1;162(11):6510–6517. [PubMed]
  • Armstrong RC, Harvath L, Dubois-Dalcq ME. Type 1 astrocytes and oligodendrocyte-type 2 astrocyte glial progenitors migrate toward distinct molecules. J Neurosci Res. 1990 Nov;27(3):400–407. [PubMed]
  • Yao J, Harvath L, Gilbert DL, Colton CA. Chemotaxis by a CNS macrophage, the microglia. J Neurosci Res. 1990 Sep;27(1):36–42. [PubMed]
  • Foreman KE, Vaporciyan AA, Bonish BK, Jones ML, Johnson KJ, Glovsky MM, Eddy SM, Ward PA. C5a-induced expression of P-selectin in endothelial cells. J Clin Invest. 1994 Sep;94(3):1147–1155. [PMC free article] [PubMed]
  • Mulligan MS, Schmid E, Till GO, Hugli TE, Friedl HP, Roth RA, Ward PA. C5a-dependent up-regulation in vivo of lung vascular P-selectin. J Immunol. 1997 Feb 15;158(4):1857–1861. [PubMed]
  • Kilgore KS, Ward PA, Warren JS. Neutrophil adhesion to human endothelial cells is induced by the membrane attack complex: the roles of P-selectin and platelet activating factor. Inflammation. 1998 Dec;22(6):583–598. [PubMed]
  • Low PJ, Ai R, Ogata RT. Active sites in complement components C5 and C3 identified by proximity to indels in the C3/4/5 protein family. J Immunol. 1999 Jun 1;162(11):6580–6588. [PubMed]
  • Rogers J, Cooper NR, Webster S, Schultz J, McGeer PL, Styren SD, Civin WH, Brachova L, Bradt B, Ward P, et al. Complement activation by beta-amyloid in Alzheimer disease. Proc Natl Acad Sci U S A. 1992 Nov 1;89(21):10016–10020. [PubMed]
  • Jiang H, Burdick D, Glabe CG, Cotman CW, Tenner AJ. beta-Amyloid activates complement by binding to a specific region of the collagen-like domain of the C1q A chain. J Immunol. 1994 May 15;152(10):5050–5059. [PubMed]
  • Velazquez P, Cribbs DH, Poulos TL, Tenner AJ. Aspartate residue 7 in amyloid beta-protein is critical for classical complement pathway activation: implications for Alzheimer's disease pathogenesis. Nat Med. 1997 Jan;3(1):77–79. [PubMed]
  • Bradt BM, Kolb WP, Cooper NR. Complement-dependent proinflammatory properties of the Alzheimer's disease beta-peptide. J Exp Med. 1998 Aug 3;188(3):431–438. [PMC free article] [PubMed]
  • Meri S, Pangburn MK. A mechanism of activation of the alternative complement pathway by the classical pathway: protection of C3b from inactivation by covalent attachment to C4b. Eur J Immunol. 1990 Dec;20(12):2555–2561. [PubMed]
  • Matsushita M. The lectin pathway of the complement system. Microbiol Immunol. 1996;40(12):887–893. [PubMed]
  • Matis LA, Rollins SA. Complement-specific antibodies: designing novel anti-inflammatories. Nat Med. 1995 Aug;1(8):839–842. [PubMed]
  • Kirk AD, Burkly LC, Batty DS, Baumgartner RE, Berning JD, Buchanan K, Fechner JH, Jr, Germond RL, Kampen RL, Patterson NB, et al. Treatment with humanized monoclonal antibody against CD154 prevents acute renal allograft rejection in nonhuman primates. Nat Med. 1999 Jun;5(6):686–693. [PubMed]
  • Rollins SA, Matis LA, Springhorn JP, Setter E, Wolff DW. Monoclonal antibodies directed against human C5 and C8 block complement-mediated damage of xenogeneic cells and organs. Transplantation. 1995 Dec 15;60(11):1284–1292. [PubMed]
  • Fodor WL, Rollins SA, Guilmette ER, Setter E, Squinto SP. A novel bifunctional chimeric complement inhibitor that regulates C3 convertase and formation of the membrane attack complex. J Immunol. 1995 Nov 1;155(9):4135–4138. [PubMed]
  • Rooney IA, Heuser JE, Atkinson JP. GPI-anchored complement regulatory proteins in seminal plasma. An analysis of their physical condition and the mechanisms of their binding to exogenous cells. J Clin Invest. 1996 Apr 1;97(7):1675–1686. [PMC free article] [PubMed]
  • Stahel PF, Barnum SR. Bacterial meningitis: complement gene expression in the central nervous system. Immunopharmacology. 1997 Dec;38(1-2):65–72. [PubMed]
  • Barker MD, Monk PN. Structure-function relationships of leucocyte chemoattractant receptors. Biochem Soc Trans. 1997 Aug;25(3):1027–1031. [PubMed]
  • Crass T, Ames RS, Sarau HM, Tornetta MA, Foley JJ, Köhl J, Klos A, Bautsch W. Chimeric receptors of the human C3a receptor and C5a receptor (CD88). J Biol Chem. 1999 Mar 26;274(13):8367–8370. [PubMed]
  • Klickstein LB, Wong WW, Smith JA, Weis JH, Wilson JG, Fearon DT. Human C3b/C4b receptor (CR1). Demonstration of long homologous repeating domains that are composed of the short consensus repeats characteristics of C3/C4 binding proteins. J Exp Med. 1987 Apr 1;165(4):1095–1112. [PMC free article] [PubMed]
  • Krych M, Hourcade D, Atkinson JP. Sites within the complement C3b/C4b receptor important for the specificity of ligand binding. Proc Natl Acad Sci U S A. 1991 May 15;88(10):4353–4357. [PubMed]
  • Lea S, Powell R, Evans D. Crystallization and preliminary X-ray diffraction analysis of a biologically active fragment of CD55. Acta Crystallogr D Biol Crystallogr. 1999 Jun;55(Pt 6):1198–1200. [PubMed]
  • Pascual M, Duchosal MA, Steiger G, Giostra E, Pechère A, Paccaud JP, Danielsson C, Schifferli JA. Circulating soluble CR1 (CD35). Serum levels in diseases and evidence for its release by human leukocytes. J Immunol. 1993 Aug 1;151(3):1702–1711. [PubMed]
  • Weisman HF, Bartow T, Leppo MK, Marsh HC, Jr, Carson GR, Concino MF, Boyle MP, Roux KH, Weisfeldt ML, Fearon DT. Soluble human complement receptor type 1: in vivo inhibitor of complement suppressing post-ischemic myocardial inflammation and necrosis. Science. 1990 Jul 13;249(4965):146–151. [PubMed]
  • Piddlesden SJ, Storch MK, Hibbs M, Freeman AM, Lassmann H, Morgan BP. Soluble recombinant complement receptor 1 inhibits inflammation and demyelination in antibody-mediated demyelinating experimental allergic encephalomyelitis. J Immunol. 1994 Jun 1;152(11):5477–5484. [PubMed]
  • Jung S, Toyka KV, Hartung HP. Soluble complement receptor type 1 inhibits experimental autoimmune neuritis in Lewis rats. Neurosci Lett. 1995 Nov 24;200(3):167–170. [PubMed]
  • Piddlesden SJ, Jiang S, Levin JL, Vincent A, Morgan BP. Soluble complement receptor 1 (sCR1) protects against experimental autoimmune myasthenia gravis. J Neuroimmunol. 1996 Dec;71(1-2):173–177. [PubMed]
  • Swift AJ, Collins TS, Bugelski P, Winkelstein JA. Soluble human complement receptor type 1 inhibits complement-mediated host defense. Clin Diagn Lab Immunol. 1994 Sep;1(5):585–589. [PMC free article] [PubMed]
  • Scesney SM, Makrides SC, Gosselin ML, Ford PJ, Andrews BM, Hayman EG, Marsh HC., Jr A soluble deletion mutant of the human complement receptor type 1, which lacks the C4b binding site, is a selective inhibitor of the alternative complement pathway. Eur J Immunol. 1996 Aug;26(8):1729–1735. [PubMed]
  • Kalli KR, Hsu PH, Bartow TJ, Ahearn JM, Matsumoto AK, Klickstein LB, Fearon DT. Mapping of the C3b-binding site of CR1 and construction of a (CR1)2-F(ab')2 chimeric complement inhibitor. J Exp Med. 1991 Dec 1;174(6):1451–1460. [PMC free article] [PubMed]
  • Mulligan MS, Warner RL, Rittershaus CW, Thomas LJ, Ryan US, Foreman KE, Crouch LD, Till GO, Ward PA. Endothelial targeting and enhanced antiinflammatory effects of complement inhibitors possessing sialyl Lewisx moieties. J Immunol. 1999 Apr 15;162(8):4952–4959. [PubMed]
  • Rittershaus CW, Thomas LJ, Miller DP, Picard MD, Geoghegan-Barek KM, Scesney SM, Henry LD, Sen AC, Bertino AM, Hannig G, et al. Recombinant glycoproteins that inhibit complement activation and also bind the selectin adhesion molecules. J Biol Chem. 1999 Apr 16;274(16):11237–11244. [PubMed]
  • Christiansen D, Milland J, Thorley BR, McKenzie IF, Loveland BE. A functional analysis of recombinant soluble CD46 in vivo and a comparison with recombinant soluble forms of CD55 and CD35 in vitro. Eur J Immunol. 1996 Mar;26(3):578–585. [PubMed]
  • Higgins PJ, Ko JL, Lobell R, Sardonini C, Alessi MK, Yeh CG. A soluble chimeric complement inhibitory protein that possesses both decay-accelerating and factor I cofactor activities. J Immunol. 1997 Mar 15;158(6):2872–2881. [PubMed]
  • Kim YU, Kinoshita T, Molina H, Hourcade D, Seya T, Wagner LM, Holers VM. Mouse complement regulatory protein Crry/p65 uses the specific mechanisms of both human decay-accelerating factor and membrane cofactor protein. J Exp Med. 1995 Jan 1;181(1):151–159. [PMC free article] [PubMed]
  • Quigg RJ, He C, Lim A, Berthiaume D, Alexander JJ, Kraus D, Holers VM. Transgenic mice overexpressing the complement inhibitor crry as a soluble protein are protected from antibody-induced glomerular injury. J Exp Med. 1998 Oct 5;188(7):1321–1331. [PMC free article] [PubMed]
  • Sahu A, Kay BK, Lambris JD. Inhibition of human complement by a C3-binding peptide isolated from a phage-displayed random peptide library. J Immunol. 1996 Jul 15;157(2):884–891. [PubMed]
  • Nilsson B, Larsson R, Hong J, Elgue G, Ekdahl KN, Sahu A, Lambris JD. Compstatin inhibits complement and cellular activation in whole blood in two models of extracorporeal circulation. Blood. 1998 Sep 1;92(5):1661–1667. [PubMed]
  • Fiane AE, Mollnes TE, Videm V, Hovig T, Høgåsen K, Mellbye OJ, Spruce L, Moore WT, Sahu A, Lambris JD. Prolongation of ex vivo-perfused pig xenograft survival by the complement inhibitor Compstatin. Transplant Proc. 1999 Feb-Mar;31(1-2):934–935. [PubMed]
  • Evans MJ, Rollins SA, Wolff DW, Rother RP, Norin AJ, Therrien DM, Grijalva GA, Mueller JP, Nye SH, Squinto SP, et al. In vitro and in vivo inhibition of complement activity by a single-chain Fv fragment recognizing human C5. Mol Immunol. 1995 Nov;32(16):1183–1195. [PubMed]
  • Wang Y, Rollins SA, Madri JA, Matis LA. Anti-C5 monoclonal antibody therapy prevents collagen-induced arthritis and ameliorates established disease. Proc Natl Acad Sci U S A. 1995 Sep 12;92(19):8955–8959. [PubMed]
  • Wang Y, Hu Q, Madri JA, Rollins SA, Chodera A, Matis LA. Amelioration of lupus-like autoimmune disease in NZB/WF1 mice after treatment with a blocking monoclonal antibody specific for complement component C5. Proc Natl Acad Sci U S A. 1996 Aug 6;93(16):8563–8568. [PubMed]
  • Thomas TC, Rollins SA, Rother RP, Giannoni MA, Hartman SL, Elliott EA, Nye SH, Matis LA, Squinto SP, Evans MJ. Inhibition of complement activity by humanized anti-C5 antibody and single-chain Fv. Mol Immunol. 1996 Dec;33(17-18):1389–1401. [PubMed]
  • Vakeva AP, Agah A, Rollins SA, Matis LA, Li L, Stahl GL. Myocardial infarction and apoptosis after myocardial ischemia and reperfusion: role of the terminal complement components and inhibition by anti-C5 therapy. Circulation. 1998 Jun 9;97(22):2259–2267. [PubMed]
  • Würzner R, Schulze M, Happe L, Franzke A, Bieber FA, Oppermann M, Götze O. Inhibition of terminal complement complex formation and cell lysis by monoclonal antibodies. Complement Inflamm. 1991;8(5-6):328–340. [PubMed]
  • Brüggemann M, Taussig MJ. Production of human antibody repertoires in transgenic mice. Curr Opin Biotechnol. 1997 Aug;8(4):455–458. [PubMed]
  • Discipio RG, Jenner L, Thirup S, Sottrup-Jensen L, Nyborg J, Stura E. Crystallization of human complement component C5. Acta Crystallogr D Biol Crystallogr. 1998 Jul 1;54(Pt 4):643–646. [PubMed]
  • Hays SJ. Therapeutic approaches to the treatment of neuroinflammatory diseases. Curr Pharm Des. 1998 Aug;4(4):335–348. [PubMed]
  • Hays SJ, Caprathe BW, Gilmore JL, Amin N, Emmerling MR, Michael W, Nadimpalli R, Nath R, Raser KJ, Stafford D, et al. 2-amino-4H-3,1-benzoxazin-4-ones as inhibitors of C1r serine protease. J Med Chem. 1998 Mar 26;41(7):1060–1067. [PubMed]
  • Plummer JS, Cai C, Hays SJ, Gilmore JL, Emmerling MR, Michael W, Narasimhan LS, Watson MD, Wang K, Nath R, et al. Benzenesulfonamide derivatives of 2-substituted 4H-3,1-benzoxazin-4-ones and benzthiazin-4-ones as inhibitors of complement C1r protease. Bioorg Med Chem Lett. 1999 Mar 22;9(6):815–820. [PubMed]
  • Rossi V, Gaboriaud C, Lacroix M, Ulrich J, Fontecilla-Camps JC, Gagnon J, Arlaud GJ. Structure of the catalytic region of human complement protease C1s: study by chemical cross-linking and three-dimensional homology modeling. Biochemistry. 1995 Jun 6;34(22):7311–7321. [PubMed]
  • Lacroix M, Rossi V, Gaboriaud C, Chevallier S, Jaquinod M, Thielens NM, Gagnon J, Arlaud GJ. Structure and assembly of the catalytic region of human complement protease C1r: a three-dimensional model based on chemical cross-linking and homology modeling. Biochemistry. 1997 May 27;36(21):6270–6282. [PubMed]
  • Narayana SV, Carson M, el-Kabbani O, Kilpatrick JM, Moore D, Chen X, Bugg CE, Volanakis JE, DeLucas LJ. Structure of human factor D. A complement system protein at 2.0 A resolution. J Mol Biol. 1994 Jan 14;235(2):695–708. [PubMed]
  • Jing H, Macon KJ, Moore D, DeLucas LJ, Volanakis JE, Narayana SV. Structural basis of profactor D activation: from a highly flexible zymogen to a novel self-inhibited serine protease, complement factor D. EMBO J. 1999 Feb 15;18(4):804–814. [PubMed]
  • Taylor FR, Bixler SA, Budman JI, Wen D, Karpusas M, Ryan ST, Jaworski GJ, Safari-Fard A, Pollard S, Whitty A. Induced fit activation mechanism of the exceptionally specific serine protease, complement factor D. Biochemistry. 1999 Mar 2;38(9):2849–2859. [PubMed]
  • Cole LB, Kilpatrick JM, Chu N, Babu YS. Structure of 3,4-dichloroisocoumarin-inhibited factor D. Acta Crystallogr D Biol Crystallogr. 1998 Sep 1;54(Pt 5):711–717. [PubMed]
  • Drapeau G, Brochu S, Godin D, Levesque L, Rioux F, Marceau F. Synthetic C5a receptor agonists. Pharmacology, metabolism and in vivo cardiovascular and hematologic effects. Biochem Pharmacol. 1993 Mar 24;45(6):1289–1299. [PubMed]
  • Konteatis ZD, Siciliano SJ, Van Riper G, Molineaux CJ, Pandya S, Fischer P, Rosen H, Mumford RA, Springer MS. Development of C5a receptor antagonists. Differential loss of functional responses. J Immunol. 1994 Nov 1;153(9):4200–4205. [PubMed]
  • Kaneko Y, Okada N, Baranyi L, Azuma T, Okada H. Antagonistic peptides against human anaphylatoxin C5a. Immunology. 1995 Sep;86(1):149–154. [PubMed]
  • Pellas TC, Boyar W, van Oostrum J, Wasvary J, Fryer LR, Pastor G, Sills M, Braunwalder A, Yarwood DR, Kramer R, et al. Novel C5a receptor antagonists regulate neutrophil functions in vitro and in vivo. J Immunol. 1998 Jun 1;160(11):5616–5621. [PubMed]
  • Heller T, Hennecke M, Baumann U, Gessner JE, zu Vilsendorf AM, Baensch M, Boulay F, Kola A, Klos A, Bautsch W, et al. Selection of a C5a receptor antagonist from phage libraries attenuating the inflammatory response in immune complex disease and ischemia/reperfusion injury. J Immunol. 1999 Jul 15;163(2):985–994. [PubMed]
  • Kretzschmar T, Pohl M, Casaretto M, Przewosny M, Bautsch W, Klos A, Saunders D, Köhl J. Synthetic peptides as antagonists of the anaphylatoxin C3a. Eur J Biochem. 1992 Nov 15;210(1):185–191. [PubMed]
  • Pohl M, Ambrosius D, Grötzinger J, Kretzschmar T, Saunders D, Wollmer A, Brandenburg D, Bitter-Suermann D, Höcker H. Cyclic disulfide analogues of the complement component C3a. Synthesis and conformational investigations. Int J Pept Protein Res. 1993 Apr;41(4):362–375. [PubMed]
  • Abbott NJ, Romero IA. Transporting therapeutics across the blood-brain barrier. Mol Med Today. 1996 Mar;2(3):106–113. [PubMed]
  • Kroll RA, Neuwelt EA. Outwitting the blood-brain barrier for therapeutic purposes: osmotic opening and other means. Neurosurgery. 1998 May;42(5):1083–1100. [PubMed]
  • Laske DW, Morrison PF, Lieberman DM, Corthesy ME, Reynolds JC, Stewart-Henney PA, Koong SS, Cummins A, Paik CH, Oldfield EH. Chronic interstitial infusion of protein to primate brain: determination of drug distribution and clearance with single-photon emission computerized tomography imaging. J Neurosurg. 1997 Oct;87(4):586–594. [PubMed]
  • Lonser RR, Gogate N, Morrison PF, Wood JD, Oldfield EH. Direct convective delivery of macromolecules to the spinal cord. J Neurosurg. 1998 Oct;89(4):616–622. [PubMed]
  • Huwyler J, Wu D, Pardridge WM. Brain drug delivery of small molecules using immunoliposomes. Proc Natl Acad Sci U S A. 1996 Nov 26;93(24):14164–14169. [PubMed]
  • Prokai-Tatrai K, Prokai L, Bodor N. Brain-targeted delivery of a leucine-enkephalin analogue by retrometabolic design. J Med Chem. 1996 Nov 22;39(24):4775–4782. [PubMed]
  • Barkats M, Bilang-Bleuel A, Buc-Caron MH, Castel-Barthe MN, Corti O, Finiels F, Horellou P, Revah F, Sabate O, Mallet J. Adenovirus in the brain: recent advances of gene therapy for neurodegenerative diseases. Prog Neurobiol. 1998 Jul;55(4):333–341. [PubMed]
  • Flax JD, Aurora S, Yang C, Simonin C, Wills AM, Billinghurst LL, Jendoubi M, Sidman RL, Wolfe JH, Kim SU, et al. Engraftable human neural stem cells respond to developmental cues, replace neurons, and express foreign genes. Nat Biotechnol. 1998 Nov;16(11):1033–1039. [PubMed]
  • Yandava BD, Billinghurst LL, Snyder EY. "Global" cell replacement is feasible via neural stem cell transplantation: evidence from the dysmyelinated shiverer mouse brain. Proc Natl Acad Sci U S A. 1999 Jun 8;96(12):7029–7034. [PubMed]

Articles from Molecular Medicine are provided here courtesy of The Feinstein Institute for Medical Research at North Shore LIJ