Researchers in the Del Monte Laboratory at the Medical University of South Carolina (MUSC) have for the first time observed defects in protein repair systems associated with unique misfolded protein plaques previously observed in patients with idiopathic dilated cardiomyopathy (IDCM).
IDCM is a heart muscle condition that may go unnoticed until the patient has advanced heart failure. The laboratory’s latest discoveries are Journal of Molecular and Cellular Cardiology The paper, an Editor’s Choice and Journal Cover selection, shows that there is a defect in the repair system for misfolded and damaged proteins. Through a comprehensive study of three major divisions of repair systems, they discovered major changes in the machinery of repair systems in major divisions. These changes are called post-translational modifications, or PTMs. They concluded that changes in the PTMs disrupted the system’s ability to respond to stress signals in misfolded proteins.
mysterious plaque
When Federica del Monte, MD, a clinical scientist at MUSC and the paper’s lead author, discovered clusters of misfolded proteins in the heart that ultimately led to the breakthrough discovery in 2010, she was working on an entirely different project.
Her experiments then showed that the heart had protein plaques similar to those found in Alzheimer’s brains.
Del Monte said the same plaques found in the brain were also present in the hearts of people with the disease.
She followed up on the research and further linked this finding to Alzheimer’s disease genes, linking Alzheimer’s disease and IDCM. (KG4)
Bring your heart and brain together
Since this discovery, the Del Monte Institute has expanded from focusing solely on the heart to include both the heart and the brain, bringing together cardiologists and neurologists to work on the next phase of research. This multidisciplinary approach revealed that before Alzheimer’s disease is seen in the brain, features of IDCM are also seen in the heart.
”We might use the heart as a window into the brain.” Del Monte said.
The opposite is also true. Del Monte’s study introduced IDCM screening to Alzheimer’s disease clinics and advocated echocardiography to detect the obvious left ventricular enlargement and weakness seen in IDCM. Camila Batchin, MD, PhD, a postdoctoral fellow at the Del Monte Institute and co-lead author of the paper, hopes that improved screening could lead to earlier treatment.
”The goal is to diagnose and treat early to prevent the disease from worsening.” she said.
The project also reflects long-term collaborations (MH5) that often drive scientific discovery. Among the co-authors is Marco Luciani, MD (MH6), who was a postdoctoral fellow at the Del Monte Institute when the project began 10 years ago and is now a faculty member at the University of Zurich. Two additional postdoctoral researchers contributed to this study. Luca Trocone, MD, currently an associate faculty member at Brigham and Women’s Hospital in Boston, and Cristina Barra, MD, currently a faculty member at the University of Ferrara in Italy.
Del Monte and Batchin highlighted the important contributions of former lab members who have contributed to the advancement of research over the years.
”Their contributions do not disappear when they leave the nest.” said Del Monte.
Their decade-long collaboration, continued across institutions and continents, ultimately helped answer the fundamental question of why plaques form in the heart.
PTMs disrupt protein repair
Because plaques are made up of misfolded proteins, Del Monte and her team focused on the systems responsible for protein repair. The team investigated not only the repair machine itself, but also the PTMs that control its activities.
”Often not the amount of protein present“Mr. Del Monte says of this system:However, if the changes that activate the protein are abnormal.”
Bacchin cited PTM as one of the study’s most revealing findings.
”PTMs seen in disease mainly caused transition to cell death” said Mr. Batchin. In other words, these modifications were causing heart cells to self-destruct. They also found that aging and Alzheimer’s disease genes exacerbate this effect.
They found that, like Alzheimer’s disease, IDCM can be considered a protein misfolding disease.
From bench to bedside, what’s next?
Looking at the entire repair system, including PTM, is a requirement moving forward, Del Monte explained. “We need to check across the board,” she said. Studying protein repair systems at their level of detail may open the door to new treatments.
”Already tested in cancer research” said Del Monte.
Batchin also said he looks forward to seeing the results of bench studies validated in clinical studies, including searching for molecular changes to identify early biomarkers of disease.
Each discovery reveals overlap between Alzheimer’s disease and heart failure, paving the way for shared diagnosis and treatment. The Del Monte Laboratory is conducting research in collaboration with fields such as cardiology, neurology, and nuclear medicine, and interdisciplinary collaboration is taking shape. And as the window between heart and brain becomes clearer, researchers are uncovering new opportunities for early diagnosis and future treatment of both diseases.
sauce:
Medical University of South Carolina
Reference magazines:
Batchin, C. Others. (2026). Cardiomyopathy and aging collectively contribute to the unfolding of assembly pathways of protein responses. Journal of Molecular and Cellular Cardiology. DOI: 10.1016/j.yjmcc.2026.03.001. https://www.jmcc-online.com/article/S0022-2828(26)00040-4/fulltext
