Therapeutic targeting of factor D and MASP3 in complement-mediated diseases: Lessons learned from mouse studies.

Autor: Mohammadyari E; Department of Systems Pharmacology and Translational Therapeutics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA., Miwa T; Department of Systems Pharmacology and Translational Therapeutics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA., Golla M; Department of Systems Pharmacology and Translational Therapeutics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA., Song WC; Department of Systems Pharmacology and Translational Therapeutics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
Jazyk: angličtina
Zdroj: European journal of immunology [Eur J Immunol] 2024 Sep; Vol. 54 (9), pp. e2350845. Date of Electronic Publication: 2024 Jun 22.
DOI: 10.1002/eji.202350845
Abstrakt: The alternative pathway (AP) plays a major role in many complement-mediated human diseases. Factor D (FD), a rate-limiting enzyme in AP complement activation, is an attractive therapeutic target. Unlike other complement proteins, FD is synthesized primarily in adipose tissue, and its levels in human blood are relatively low. However, because of FD's high turnover rate, therapeutic targeting with monoclonal antibodies and chemical inhibitors has been challenging. The recent discovery that FD activity is regulated by mannose-binding lectin-associated serine protease 3 (MASP3), through conversion of a zymogen to mature FD, has sparked interest in MASP3 inhibition as a new way to block FD function and AP complement activity. Here, we review studies of mouse models of FD and MASP3 inhibition. We additionally discuss the lessons learned from these studies and their implications for therapeutic targeting of human FD and MASP3.
(© 2024 The Author(s). European Journal of Immunology published by Wiley‐VCH GmbH.)
Databáze: MEDLINE
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