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Maremonti, F.* ; Tonnus, W.* ; Gavali, S.* ; Bornstein, S.R. ; Shah, A.* ; Giacca, M.* ; Linkermann, A.*

Ferroptosis-based advanced therapies as treatment approaches for metabolic and cardiovascular diseases.

Cell Death Differ., DOI: 10.1038/s41418-024-01350-1 (2024)
Publ. Version/Full Text DOI PMC
Open Access Gold (Paid Option)
Creative Commons Lizenzvertrag
Ferroptosis has attracted attention throughout the last decade because of its tremendous clinical importance. Here, we review the rapidly growing body of literature on how inhibition of ferroptosis may be harnessed for the treatment of common diseases, and we focus on metabolic and cardiovascular unmet medical needs. We introduce four classes of preclinically established ferroptosis inhibitors (ferrostatins) such as iron chelators, radical trapping agents that function in the cytoplasmic compartment, lipophilic radical trapping antioxidants and ninjurin-1 (NINJ1) specific monoclonal antibodies. In contrast to ferroptosis inducers that cause serious untoward effects such as acute kidney tubular necrosis, the side effect profile of ferrostatins appears to be limited. We also consider ferroptosis as a potential side effect itself when several advanced therapies harnessing small-interfering RNA (siRNA)-based treatment approaches are tested. Importantly, clinical trial design is impeded by the lack of an appropriate biomarker for ferroptosis detection in serum samples or tissue biopsies. However, we discuss favorable clinical scenarios suited for the design of anti-ferroptosis clinical trials to test such first-in-class compounds. We conclude that targeting ferroptosis exhibits outstanding treatment options for metabolic and cardiovascular diseases, but we have only begun to translate this knowledge into clinically relevant applications.
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Publication type Article: Journal article
Document type Review
Corresponding Author
Keywords Coronary-heart-disease; Ischemia-reperfusion Injury; Cell-death; Cancer-cells; Iron; Damage; Glycine; Menaquinone; Glutathione; Mortality
ISSN (print) / ISBN 1350-9047
e-ISSN 1476-5403
Journal Cell Death and Differentiation
Publisher Nature Publishing Group
Publishing Place Campus, 4 Crinan St, London, N1 9xw, England
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) Institute for Pancreatic Beta Cell Research (IPI)