Scientists at Trinity College Dublin’s School of Biochemistry and Immunology have discovered that the repression of an enzyme called Fumarate Hydratase occurs in macrophages, which play a role in various diseases such as Lupus, Arthritis, Sepsis, and COVID-19. When Fumarate Hydratase is repressed, RNA is released from mitochondria, which can bind to key proteins and trigger the release of cytokines, worsening inflammation. This knowledge could lead to the development of more effective treatments that target the underlying mechanisms of inflammatory diseases. Cedars Sinai Medical Centre in Los Angeles is a key collaborator helping with the study of Lupus patients. The study was funded by the European Research Council, Medical Research Council, and Science Foundation Ireland.
Scientists at Trinity College Dublin’s School of Biochemistry and Immunology in the Trinity Biomedical Sciences Institute have made a breakthrough in understanding the progression of inflammatory diseases. They have discovered that the suppression of an enzyme called Fumarate Hydratase occurs in macrophages, a type of inflammatory cell that plays a role in various diseases such as Lupus, Arthritis, Sepsis, and COVID-19.
The researchers found that when Fumarate Hydratase is repressed, RNA is released from mitochondria, which can bind to key proteins ‘MDA5’ and ‘TLR7’ and trigger the release of cytokines, thereby worsening inflammation. This newly published research has uncovered a promising new target for therapeutic intervention and presents an exciting prospect for badly needed new anti-inflammatory therapies.
The lead author of the research article, Professor Luke O’Neill, said that this process might be targetable to treat debilitating diseases like Lupus, a nasty autoimmune disease that damages several parts of the body including the skin, kidneys, and joints. Christian Peace, joint first-author, added that they have made an important link between Fumarate Hydratase and immune proteins called cytokines that mediate inflammatory diseases.
In the context of kidney cancer, another publication by a group led by Professor Christian Frezza, now at the University of Cologne, and Dr. Julien Prudent at the MRC Mitochondrial Biology Unit (MBU), has made similar findings. Fumarate Hydratase was shown to be repressed in a model of sepsis, a potentially life-threatening systemic inflammatory condition that can happen during bacterial and viral infections. Similarly, in blood samples from patients with Lupus, Fumarate Hydratase was dramatically decreased.
The discovery of this promising new target for therapeutic intervention in inflammatory diseases is significant because it sheds light on what goes wrong in our bodies during the progression of these diseases. This knowledge could lead to the development of more effective treatments that target the underlying mechanisms of inflammatory diseases.
The discovery of a promising new target for therapeutic intervention in inflammatory diseases could widen the scope of potential therapeutic targets beyond inflammation, according to Professor Luke O’Neill, the lead author of a new research article in the journal Nature. The study, conducted by scientists at Trinity College Dublin’s School of Biochemistry and Immunology in collaboration with eight universities, uncovered the repression of an enzyme called Fumarate Hydratase in macrophages, a type of inflammatory cell involved in various diseases such as Lupus, Arthritis, Sepsis, and COVID-19. Fumarate Hydratase was shown to be repressed in a model of sepsis, a potentially life-threatening systemic inflammatory condition that can occur during bacterial and viral infections. Similarly, in blood samples from patients with Lupus, Fumarate Hydratase was dramatically decreased. The researchers found that when Fumarate Hydratase is repressed, RNA is released from mitochondria, which can bind to key proteins ‘MDA5’ and ‘TLR7’ and trigger the release of cytokines, thereby worsening inflammation.
The study was funded by the European Research Council, Medical Research Council, and Science Foundation Ireland. Cedars Sinai Medical Centre in Los Angeles is another key collaborator helping with the study of Lupus patients. The research provides new insights into the progression of inflammatory diseases and presents an exciting prospect for badly needed new anti-inflammatory therapies. The discovery sheds light on what goes wrong in our bodies during the progression of these diseases, and the knowledge gained could lead to the development of more effective treatments that target the underlying mechanisms of inflammatory diseases.
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