The complement system (CS) is a key component of innate immunity, which is involved in several physiologic and pathologic processes. Dysregulated or impaired complement is involved in an increasing list of human diseases (e.g. autoimmune, inflammatory, and neurodegenerative diseases etc.). CS consists of over forty protein components that are present in the blood or on cell surfaces. CS is activated by infection or by injury and activation may be prolonged or misdirected to healthy cells and can lead to inflammatory or auto-immune diseases. Complement-targeted drugs could provide novel therapeutic intervention against the above diseases. Nine serine proteases are integral elements of the CS cascade (C1r, C1s, C2, MASP-1, MASP-2, MASP-3, factor D, factor B, factor I). C1s is present as a proenzyme within the C1 molecule in complex with C1q and C1r. The activation of the C1 complex is the „classical activation pathway” of CS, which is initiated by the interaction of C1q with immunoglobulin (Ig) antigen complexes. The activation signal is mechanically transmitted by C1q to C1r dimers; activated C1r proteases then cleave and activate the C1s proenzymes. Activated C1s protease forwards the activation signal by cleaving C4 and C4bassociated C2 to form C3 convertase C4b2a, so an inhibitor that targets the C1s protease domain could block the activation of the classical pathway of CS.
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