idw – Informationsdienst Wissenschaft
Nachrichten, Termine, Experten
Nachrichten, Termine, Experten
idw - Informationsdienst
Wissenschaft
When upon an ischemic event reperfusion is induced, which occurs for instance during organ transplantation or resuscitation after cardiac arrest, this reperfusion can paradoxically cause additional damage to the affected tissue. Such ischemia-reperfusion injuries (IRI) are a serious complication, responsible for a variety of clinically important conditions including stroke and acute kidney injury. Ferroptosis, a recently described form of regulated necrotic cell death, has emerged as a common underlying pathomechanism of tissue IRI, and represents a most promising therapeutic target to prevent extensive IRI-driven cell loss, tissue dysfunction and necroinflammation.
Ferroptosis is a form of cell death characterized by iron-dependent lipid peroxidation, ultimately leading to plasma membrane rupture and death of the cell. To date, there is no biomarker available that unequivocally allows for the detection of ferroptosis, and despite the development of ferroptosis inhibitors there is no treatment for IRI.
The consortium brings together six partners in Germany with highly complementary expertise in (oxi-)lipidomics, bioinformatics, drug discovery, immunology, organ transplantation, pre-clinical and clinical research in a highly interdisciplinary approach. Specifically, the researchers from Munich, Dresden, Regensburg and Essen aim to identify and validate common ferroptotic signatures and molecular mechanisms in organs mostly affected by IRI such as brain, liver, lung and kidney. Furthermore, ferroptosis-specific biomarkers are supposed to be identified that are urgently needed for clinical monitoring of disease progression and that can be used as markers to assess therapeutic success. Ultimately, the researchers strive to provide proof-of-concept for next generation ferroptosis inhibitors.
Dr. Maria Fedorova, leader of the research group “Lipid Metabolism: Analysis and Integration” at the Center of Membrane Biochemistry and Lipid Research (ZML) at the Faculty of Medicine of TUD, is the project coordinator of the FERROPath consortium (“Ferroptosis as a common underlying pathomechanism in tissue ischemia/reperfusion injury”) that will be funded by the Bundesministerium für Bildung und Forschung (BMBF) from July 2022 for 3 years. Helmholtz Munich contributes with two subprojects to this German-wide consortium: Dr. Marcus Conrad along with Dr. Bettina Proneth (Institute of Metabolism and Cell Death, MCD) are heading the subproject entitled “Modulating ferroptosis in vivo using transgenic mouse models and next generation small molecule ferroptosis inhibitors”, whereas Dr. Ali Önder Yildirim und Dr. Aicha Jeridi (Institute of Lung Health and Immunity (LHI)) are spearheading the subproject „Ferroptosis accelerates disease progression in lung transplantation IRI”.
Prof. Edward Geissler and PD Dr. Elke Eggenhofer
Klaus Völcker
UKR
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