Selective ACSL4 inhibitors to interrogate ferroptosis in Parkinson disease – FerInh4Park

Ferroptosis, first coined in 2012, is a regulated cell death (RCD) characterized by iron-dependent accumulation of lipid hydroperoxides associated with an insufficient capacity to eliminate these oxidation products. This RCD has significant implications in diverse pathologies, including Parkinson and Alzheimer’s diseases, ischemia-reperfusion injury and stroke. A recent report revealed that genetic and pharmacological inhibition of acyl-CoA synthetase long-chain 4 (ACSL4) confer an unprecedented protection against ferroptosis, hence uncovering ACSL4 as a critical contributor to ferroptosis execution. Based on solid preliminary data, the aim of the present research is to develop selective acyl-CoA synthetase long-chain 4 (ACSL4) inhibitors. These novel pharmacological tools will constitute strong basis for the future development of anti-ferroptotic agents for the treatment of ferroptosis-related diseases, including Parkinson disease.