Crohn’s Disease Research Could Benefit From discovery of Small Molecule Associated With Inflammatory Cell Death

Crohn’s Disease Research Could Benefit From discovery of Small Molecule Associated With Inflammatory Cell Death
A new study, entitled “Activation of the pseudokinase MLKL unleashes the four-helix bundle domain to induce membrane localization and necroptotic cell death” published in the journal Proceedings of the National Academy of Sciences by Dr Joanne Hildebrand, part of  Professor John Silke’s research group from Cell Signaling and Cell Death division at The Walter and Eliza Hall Institute of Medical Research in Australia, has identified a small molecule that inhibits necroptosis, a form of cell death, that induces inflammation. The new discovery may pave the way for potential new therapies for inflammatory diseases such as rheumatoid arthritis, Crohn’s disease and psoriasis. Necroptosis is considered to be complementary to the classical caspase-dependent programmed cell death pathway, while apoptosis is a recently discovered cell death pathway linked to immune disorders. It is a vital process in which cells undergo programmed death while warning the immune system that something has gone wrong, such as during viral infection. But when necroptosis is improperly activated, it can induce inflammation and the development of inflammatory diseases. Dr. Joanne Hildebrand, Ms. Maria Tanzer, and collaborators were elucidating the mechanism of killing by the protein pseudokinase Mixed Lineage Kinase Domain-Like (MLKL) through the process necroptosis. They found that a particular portion of MLKL “opens” when the protein is activated enabling the binding to the cell membrane and induce cell death. Dr Hildebrand said that, “It’s like flicking a molecular switch. We showed that when the switch can’t be ‘turned on’, MLKL doesn’t become active and necroptosis is prevented. MLKL is the final protein in the cell death pathway but it needs to be activated before i
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