A new study by the Johns Hopkins Medicine researchers has revealed how an enzyme activates and engages a "trash and recycling system" in heart cells to help patients recuperate better from a heart attack.
The study published in Nature Communications mentions that the researchers believe that this system could be transformed and used to clean up damaged and misfolded proteins that accumulate in heart cells and eventually become toxic.
The researchers ascertained that the enzyme protein kinase G, which builds up after a heart attack, impacts CHIP (carboxyl terminus of Hsc70-interacting protein), helping to move misfolded and damaged proteins to the proteasome, the "recycling plant" of the cell. Based on this finding, the researchers showed that CHIP—modified by protein kinase G or genetically changed to mimic this modification—has enhanced ability to clear the damaged proteins. Subsequently, they explain, this prevents progress to heart failure after an attack.
The discovery occurred when lead author Mark Ranek, Ph.D., assistant professor of medicine at the Johns Hopkins University School of Medicine, examined mice genetically engineered to obstruct protein kinase G from being turned on after a heart attack. He discerned that CHIP protein levels were much lower than usual, and misfolded/damaged proteins accumulated in a more significant number in the mouse hearts. It meant that CHIP was a critical factor in clearing the damaged proteins. Further confirming the connection was that blocking protein kinase G weakened CHIP's function while turning on the kinase or using mutations to mimic that it was protective.
David Kass is an M.D. and an Abraham and Virginia Weiss Professor of Cardiology at the Johns Hopkins University School of Medicine. He says, "Because CHIP is so small and simple to work with, we believe that it will be probable to develop its genetic mutation form into gene therapy. We can use that to treat not only the heart disease but also diseases like Alzheimer's or Parkinson's, that also result from the buildup of misfolded proteins, but in this situation in the brain."
Kass and his team have registered for a patent concerning the development of such a therapy.
What is Gene Therapy?
Gene therapy is the procedure of inserting genes into an individual's cells and tissues to cure a disease, such as a hereditary disease. A functional one replaces a deleterious mutant allele. Although the technology is still in its initial phase, it has shown some success. Antisense therapy is not strictly a form of gene therapy but is a genetically-mediated therapy and is often considered together with other methods.
What are the damaged proteins?
Oxidative modification and other forms of damage through oxidative stress, disease, and aging affect the cellular proteins. This oxidative damage results in loss and or change of protein function, compromising cell function, and may even cause cell death.
Therefore, the removal of damaged proteins is essential for the maintenance of normal cell function. The 20S Proteasome functions primarily as a system for the removal of such damaged proteins.