A new study has found that erectile dysfunction drugs – sildenafil and tadalafil – can help destroy misfolded proteins or toxic proteins that wreak havoc on healthy cells, tissues, and organs.
The accumulation of these misfolded proteins can be seen in a variety of disorders, especially neurodegenerative diseases such as Alzheimer’s and Parkinson’s.
The study found that sildenafil and tadalafil, which belong to a class of erectile dysfunction drugs called PDE5-inhibitors, could help destroy these toxic proteins, suggesting that they can help treat Alzheimer’s and Parkinson’s.
Researchers at Harvard Medical School described how sildenafil and tadalafil lowered the deposition of the misfolded proteins and reduced cell death in the Proceedings of the National Academy of Sciences.
Senior study author Alfred Goldberg said, “Our study indicates a new approach to combat the basic cause of many neurodegenerative diseases as well as certain rare cardiac and muscle diseases, which are due to the buildup of misfolded intracellular proteins.”
“Hopefully, these findings will lead to novel therapies in the coming years,” he added.
First author of the study Jordan VerPlank said, “By turning on the cell’s garbage disposal system, this widely prescribed class of drug could have a beneficial effect against disorders involving misfolded proteins. We now have a new point of entry to explore ways to treat or slow the progression of these diseases.”
The researchers were intrigued by evidence that PDE5 inhibitors can increase the degradation of a mutant protein that causes rare inherited heart disease, a type of cardiomyopathy.
However, the researchers cautioned that these findings do not suggest that sildenafil and tadalafil are an immediate treatment for Alzheimer’s and Parkinson’s.
Goldberg said, “These results are very promising but it will be necessary to determine the best and safest way to pharmacologically raise cGMP levels in the brain and to determine at what stage of the disease this approach may be of benefit.”
“At the cell and molecular level, we have uncovered new ways that cells have to regulate their protein composition,” Goldberg said. “But it is quite unclear how putting a small phosphate group on the very large proteasome particle can accelerate its function and alter cell protein composition,” he added. “So, there’s a lot to be explored.”
