Host: The Japanese Pharmacological Society
Name : The 96th Annual Meeting of the Japanese Pharmacological Society
Number : 96
Location : [in Japanese]
Date : November 30, 2022 - December 03, 2022
Pathology-dependent protein-protein interactions (PPIs) have been attracted attention as a new drug target, since this strategy is expected to reduce the risk of adverse effect caused by chronic drug treatment. Our group investigated the molecular mechanism underlying the development of cardiac remodeling, especially focusing on myocardial stiffness associated with fibrosis and myocardial early senescence associated with mitochondrial abnormality and oxidative stress. The pathology-dependent formation of PPIs is revealed to involve post-translational (redox-dependent) modifications of target proteins or the escape of target proteins from endoplasmic reticulum-associated degradation (ERAD) system. We performed drug screenings to inhibit these PPIs, using approved drugs whose efficacy and safety are guaranteed by Japanese government. In fact, pharmacological disruption of pathology-dependent PPIs was found to improve chronic heart failure in mice. These results strongly suggest that targeting pathology-dependent PPIs using approved drugs will become a breakthrough strategy for the treatment of intractable cardiovascular diseases.
