The critical roles of protein quality control systems in the pathogenesis of heart failure.

Yasuhiro Maejima

Journal of cardiology 2020 Mar

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Heart failure is a refractory disease with a prevalence that has continuously increased around the world. Over the past decade, we have made remarkable progress in the treatment of heart failure, including drug therapies, device therapies, and regeneration therapies. However, as each of these heart failure therapies does not go much beyond symptomatic therapy, there is a compelling need to establish novel therapeutic strategies for heart failure in a fundamental way. As cardiomyocytes are terminally differentiated cells, protein quality control is critical for maintaining cellular homeostasis, optimal performance, and longevity. There are five evolutionarily conserved mechanisms for ensuring protein quality control in cells: the ubiquitin-proteasome system, autophagy, the unfolded protein response, SUMOylation, and NEDDylation. Recent research has clarified the molecular mechanism underlying how these processes degrade misfolded proteins and damaged organelles in cardiomyocytes. In addition, a growing body of evidence suggests that deviation from appropriate levels of protein quality control causes cellular dysfunction and death, which in turn leads to heart failure. We herein review recent advances in understanding the role of protein quality control systems in heart disease and discuss the therapeutic potential of modulating protein quality control systems in the human heart. Copyright © 2019. Published by Elsevier Ltd.

Citation

Yasuhiro Maejima. The critical roles of protein quality control systems in the pathogenesis of heart failure. Journal of cardiology. 2020 Mar;75(3):219-227