Itaconate: A Potential Therapeutic Strategy for Autoimmune Disease.

Abstract

Itaconate is a metabolite of the Krebs cycle, and endogenous itaconate is driven by a variety of innate signals that inhibit the production of inflammatory cytokines. The key mechanism of action of itaconate was initially found to be the competitive inhibition of succinate dehydrogenase (SDH), which inhibits the production of inflammatory factors, as well as its antioxidant effects. With increasing research, it was discovered that it modifies cysteine residues of related proteins through the Michael addition, such as modifying the Kelch-like ECH-associated protein 1 (KEAP1) protein and activating the nuclear factor erythroid 2-related factor 2 (NRF2) signalling pathway, as well as glycolytic enzymes and cellular pathway-associated factors that attenuate inflammatory responses and oxidative stress. It also acts on a variety of immune cells, affecting their function and activity, and has been increasingly shown to play a therapeutic role in a variety of inflammatory and autoimmune diseases through a combination of these mechanisms. In conclusion, there has been a great breakthrough in the research of itaconate, from the initial industrial application to the redefinition of the biological functions of itaconate. However, with the deepening of the research, we also found that there are more questions: the mechanism of action of itaconate, more functions of itaconate, clinical application of itaconate, and the use of itaconate still needs to be solved.