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The aberrant buildup of misfolded proteins is associated with a large host of disorders, including Alzheimer's and Parkinson's. Aggregates of these toxic proteins continue to be extremely damaging to the function of cells, tissues, and organs, despite intensive research over decades on the subject.
Now, in a new study, researchers from Harvard Medical School say they may have found an unexpected method for preventing the accumulation of these toxic proteins in humans — a drug commonly used to treat erectile dysfunction.
Activating the protein quality-control system
In the researchers' study, published in Proceedings of the National Academy of Sciences, they identified a new mechanism for activating the protein quality-control system of cells and improving their ability to dispose of misfolded proteins, including ones that are known to cause neurodegenerative diseases.
The researchers detail how PDE5 inhibitors — such as erectile dysfunction drugs sildenafil and tadalafil — lower the accumulation of these mutant proteins in zebrafish models of neurodegeneration. In doing so, they also reduced cell death and anatomical defects in the models.
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"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," senior study author Alfred Goldberg, professor of cell biology in the Blavatnik Institute at HMS, said in a press release.
Potential for novel therapies
The approach is attractive as a treatment as it uses a previously unknown mechanism that cells naturally possess, which remodels their protein composition through increased degradation.
"Hopefully, these findings will lead to novel therapies in the coming years," Goldberg added.
In other recent developments, researchers have recently been using the microgravity conditions aboard the International Space Station to study a protein associated with Alzheimer's, and scientists developed a nasal vaccine that may help to treat the degenerative disease.