Regulated necrosis: disease relevance and therapeutic opportunities
The Norwegian PhD School of Heart Research (Norheart) welcomes all interested to a guest lecture given by Professor Peter Vandenabeele, a world expert on cell death.
The discovery of regulated cell death has created many possibilities for gaining control over the life and death decisions made by cells in a wide variety of inflammatory, degenerative and infectious diseases. For many years, apoptosis has been the focus of drug discovery. However, cell death research recently identified regulatory mechanisms and signaling pathways of non-apoptotic forms of regulated cell death, called regulated necrosis including necroptosis, parthanatos, cyclophilin-D-mediated necrosis, ferroptosis or oxytosis, MPT-dependent necrosis, pyroptosis and pyronecrosis, and NETosis/ETosis. Regulated necrosis (RN) is now defined as a genetically controlled cell death process morphologically characterized by cytoplasmic granulation, cellular swelling (“oncosis”), eventually resulting in plasma membrane permeabilization. The talk focuses on the mechanisms that regulate the pro-survival and pro-cell death function of RIPK1 kinase during apoptosis and necroptosis in vitro and in vivo. I will also briefly discuss the execution mechanism of necroptosis involving MLKL. In addition, I will briefly summarize the discovery of small molecules that can inhibit these non-apoptotic forms of cell death and how their availability will allow better mechanistic understanding of the cell death process itself, appreciation of the contribution of cell death in experimental disease models and the development of new therapeutic strategies, such as combined targeting of multiple types of necrotic cell death. Altogether targeting necrotic cell death has created now a second big wave of expectations, after apoptosis targeting, in translating the fundamental understanding of cell death pathways into the clinic in a broad domain of inflammatory, degenerative, infectious diseases and cancer therapy.
About the speaker
With more than 300 published articles and over 25 000 citations, Professor Peter Vandenabeele is a world expert on cell death, with a special focus on regulated necrosis, defined as necroptosis.