Ferroptosis, a term introduced in 2012, is an iron-dependent regulated cell death marked by the buildup of toxic levels of lipid peroxides. Ongoing investigations are assessing this mechanism as a potential target for various diseases, including Parkinson’s Disease. The link between ferroptosis and alpha-synuclein was recently published by Prof. D. Devos’ team from our center.

Recent findings have identified acyl-CoA synthetase long-chain 4 (ACSL4) as a pivotal participant in ferroptosis execution. Consequently, ACSL4 inhibitors are emerging as attractive anti-ferroptotic agents with therapeutic potential in cancer and neurodegenerative diseases. Since the initiation of this project, we established crucial tools and methods integral to the project's advancement, including the production of human ACSL4, the implementation of orthogonal enzymatic and biophysical assays (TSA, MST, NMR), the development of ferroptosis cell-based assays and the identification of novel inhibitors. Several families of original and potent molecules are under study.