Researchers in the del Monte Lab at the Medical University of South Carolina have identified defects in the cellular system that repairs misfolded proteins in idiopathic dilated cardiomyopathy (IDCM), a heart muscle disease that often stays silent until patients reach advanced heart failure. The findings, published in the Journal of Molecular and Cellular Cardiology, were selected as an editor's choice and featured on the journal cover.
The team examined all three major branches of the protein repair system and found alterations in the machinery of the main branches. Those alterations, known as post-translational modifications, are chemical changes to proteins after they are made. The researchers concluded that the shifts in these modifications blunted the system's ability to respond to stress signals generated by misfolded proteins - in other words, the cellular cleanup crew was still present but no longer reacting properly to the alarm.
The link to dementia research runs through Federica del Monte, M.D., Ph.D., the MUSC clinician-scientist and senior author on the paper. While working on an unrelated project, she found clusters of misfolded proteins in the heart, a finding that led to her landmark 2010 discovery: protein plaques in cardiac tissue that resembled the plaques seen in the brains of people with Alzheimer's disease.
That resemblance is what makes this work relevant beyond cardiology. If the same repair machinery falters in both organs, then the misfolded protein deposits described in failing hearts may share mechanisms with those in the aging brain. For now, the study identifies where the repair system breaks down in IDCM, which gives researchers a concrete target to interrogate as they test whether the parallel between heart and brain runs deeper than appearance.