The potential of gamma secretase as a therapeutic target for cardiac diseases

Abstract

Heart diseases are some of the most common and pressing threats to human health worldwide. The American Heart Association and the National Institute of Health jointly work to annually update data on cardiac diseases. In 2018, 126.9 million Americans were reported as having some form of cardiac disorder, with an estimated direct and indirect total cost of USD 363.4 billion. This necessitates developing therapeutic interventions for heart diseases to improve human life expectancy and economic relief. In this review, we look into gamma-secretase as a potential therapeutic target for cardiac diseases. Gamma-secretase, an aspartyl protease enzyme, is responsible for the cleavage and activation of a number of substrates that are relevant to normal cardiac development and function as found in mutation studies. Some of these substrates are involved in downstream signaling processes and crosstalk with pathways relevant to heart diseases. Most of the substrates and signaling events we explored were found to be potentially beneficial to maintain cardiac function in diseased conditions. This review presents an updated overview of the current knowledge on gamma-secretase processing of cardiac-relevant substrates and seeks to understand if the modulation of gamma-secretase activity would be beneficial to combat cardiac diseases.