Investigating the role of ferroptosis in acute liver injury and multiple sclerosis with newly developed chemical tool compounds.

Cell death research was revitalized by the understanding that necrosis can occur in a highly regulated and genetically controlled manner. Necrotic cell death is a kind of cell death in which cells release their cellular content in the surrounding tissue, in contrast to apoptotic cell death. We now realize that multiple forms of regulated necrosis exist. A new type of regulated necrosis that is catalysed by iron was recently unravelled and is now referred to as ferroptosis. Several hereditary conditions have been found that perturb body iron homeostasis and promote pathological deposition of the metal resulting in organ damage in liver, heart, pancreas, thyroid and the central nervous system. For this reason, iron chelators have been implemented or proposed as treatments for these diseases. Because iron is an essential metal for the overall functioning of organisms, whole body scavenging of iron is not preferable due to its expected detrimental side effects. In view of the recent experimental findings that inhibitors of ferroptosis (called ferrostatins) can protect against degenerative diseases, we want to unravel the molecular mechanisms involved in ferroptosis in more detail, identify new ferroptosis inhibitors that can be used in vivo, and validate them in cellular assays and mouse models.

Keywords:MULTIPLE SCLEROSIS

Disciplines:Organic chemistry, Laboratory medicine, Medical systems biology, Biomarker discovery and evaluation, Drug discovery and development, Medicinal chemistry, Medicinal products, Pharmaceutics, Pharmacognosy and phytochemistry, Pharmacology, Pharmacotherapy, Toxicology and toxinology, Other pharmaceutical sciences

Project type:Collaboration project