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Updated: Jan 4, 2026
Assays for the Degradation of Misfolded Proteins in Cells
Published on: August 28, 2016
The critical roles of protein quality control systems in the pathogenesis of heart failure
1Department of Cardiovascular Medicine, Tokyo Medical and Dental University, Tokyo, Japan.
Insights
Protein quality control is vital for heart health. Dysregulation of these systems contributes to heart failure, suggesting new therapeutic targets for this refractory disease.
Area of Science:
- Cardiology
- Molecular Biology
- Cellular Homeostasis
Background:
- Heart failure is a global health challenge with increasing prevalence.
- Current treatments primarily offer symptomatic relief, highlighting the need for fundamental therapeutic strategies.
- Cardiomyocytes rely on robust protein quality control (PQC) for cellular function and survival.
Purpose of the Study:
- To review recent advances in understanding the role of PQC systems in heart disease.
- To discuss the therapeutic potential of modulating PQC systems for heart failure treatment.
Main Methods:
- Review of current scientific literature on protein quality control mechanisms.
- Analysis of the link between PQC dysfunction and cardiomyocyte pathology.
- Exploration of PQC pathways including the ubiquitin-proteasome system, autophagy, unfolded protein response, SUMOylation, and NEDDylation.
Main Results:
- PQC is essential for maintaining cardiomyocyte homeostasis, performance, and longevity.
- Five conserved PQC mechanisms ensure cellular health: ubiquitin-proteasome system, autophagy, unfolded protein response, SUMOylation, and NEDDylation.
- Disruptions in PQC contribute to cellular dysfunction, death, and the development of heart failure.
Conclusions:
- Protein quality control systems play a critical role in preventing and potentially treating heart failure.
- Targeting PQC pathways represents a promising novel therapeutic strategy for heart failure.
- Further research into PQC modulation could lead to fundamental advancements in cardiovascular medicine.
Abstract:
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.
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