Scientists study protective mechanisms of cells from oxidative stress
A group of researchers from 每日大赛 in collaboration with scientists from Trinity College Dublin, St. Petersburg State University and the Institute of Experimental Medicine (St. Petersburg) have discovered new approaches
Co-authors from KFU are Head of the Industrial Biopharmaceutics Laboratory of the Institute of Fundamental Medicine and Biology, Lead Researcher Emil Bulatov and Junior Researcher of the Biomedical Technologies Laboratory Raniya Khadiullina.
The central topic of the study was the NRF2 protein, a key element of antioxidant protection of cells. Normally, its activity is strictly controlled by degradation through the ubiquitination system, but under conditions of oxidative stress, the protein is activated, stimulating protective genes such as HMOX1 and NQO1. Scientists have demonstrated that cyclic vinyl sulfones, synthetic molecules first described by Russian chemists in the 1990s, can effectively stabilize NRF2 by blocking its degradation. One of the compounds studied, LCB1353, demonstrated the ability to protect cells from ferroptosis, a specific type of cell death caused by the accumulation of reactive oxygen species.
鈥淥ur study has shown for the first time that these compounds can be used to develop drugs aimed at combating inflammatory and degenerative diseases, such as chronic obstructive pulmonary disease and acute inflammation,鈥� Bulatov noted.
In addition to studying the biological effects, the team synthesized and studied in detail the mechanism of action of vinyl sulfones. It turned out that the compounds selectively modify key regions of the KEAP1 protein, which is responsible for suppressing NRF2, thus ensuring the activation of antioxidant pathways. These data open up prospects for the creation of safe and highly effective compounds for pharmaceutical use.