C1, MBL-MASPs and C1-inhibitor: novel approaches for targeting complement-mediated inflammation

László Beinrohr, J. Dobó, P. Závodszky, P. Gál

Research output: Contribution to journalArticle

40 Citations (Scopus)

Abstract

Complement activation is initiated by the pattern-recognition molecules complement component C1q, mannose-binding lectin (MBL) and ficolins (H-, L-, M-ficolin), which typically recognize antibody-antigen complexes or foreign polysaccharides. The associated proteases (C1r, C1s, MASP-1 and MASP-2) then activate the complement system. The serpin C1-inhibitor (C1-inh) blocks activity of all these complexes and has been successfully used in models of disease. Many structures of these components became available recently, including that of C1-inh, facilitating the structure-guided design of drugs targeting complement activation. Here, we propose an approach in which therapeutic proteins are made up of natural protein domains and C1-inh to allow targeting to the site of inflammation and more specific inhibition of complement activation. In particular, engineering a fast-acting C1-inh or fusing it to an 'aiming module' has been shown to be feasible and economical using a humanized yeast expression system. Complement-mediated inflammation has been linked to ischemia-reperfusion injury, organ graft rejection and even neurodegeneration, so targeting this process has direct clinical implications.

Original languageEnglish
Pages (from-to)511-521
Number of pages11
JournalTrends in Molecular Medicine
Volume14
Issue number12
DOIs
Publication statusPublished - Dec 2008

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Mannose-Binding Protein-Associated Serine Proteases
Mannose-Binding Lectin
Complement Activation
Inflammation
Complement C1q
Antithrombin III
Graft Rejection
Drug Delivery Systems
Antigen-Antibody Complex
Reperfusion Injury
Polysaccharides
Peptide Hydrolases
Yeasts
Transplants
ficolin
Proteins
Therapeutics

ASJC Scopus subject areas

  • Molecular Biology
  • Molecular Medicine

Cite this

C1, MBL-MASPs and C1-inhibitor : novel approaches for targeting complement-mediated inflammation. / Beinrohr, László; Dobó, J.; Závodszky, P.; Gál, P.

In: Trends in Molecular Medicine, Vol. 14, No. 12, 12.2008, p. 511-521.

Research output: Contribution to journalArticle

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