Researchers have found that aspirin may help pulverize an enzyme linked to neurodegenerative conditions like Alzheimer’s, Parkinson’s and Huntington’s diseases— suggesting that taking the common drug may help reduce Americans’ disease risk. In their research, published this week in the journal PLOS One, study authors at Johns Hopkins University and Boyce Thompson Institute discovered that salicylic acid, a byproduct of aspirin, binds to the enzyme GAPDH (Glyceraldehyde 3-Phosphate Dehydrogenase), preventing it from moving into a cell’s nucleus where it would cause cell death.
During oxidative stress, GAPDH is affected then enters the nucleus of neurons, where it affects protein turnover and leads to cell death, causing neurodegenerative loss. The anti-Parkinson's drug deprenyl already demonstrates GAPDH's ability to prevent entry into the nucleus and the corresponding cell death, according to a news release.
"The new study establishes that GAPDH is a target for salicylate drugs related to aspirin, and hence may be relevant to the therapeutic actions of such drugs,” co-author Solomon Snyder, professor of neuroscience at Johns Hopkins University in Baltimore, said in the release.
Snyder, along with senior author Daniel Klessig, a professor at Boyce Thompson Institute and Cornell University, used high-throughput screens to find proteins in the human body that bind to salicylic acid. GAPDH primarily plays a role in glucose metabolism, but it also helps regulate plants’ immune systems. Past research suggests several targets in plants are affected by salicylic acid and that many are translatable to humans, according to the release.
In the current study, scientists also observed that a natural derivative of salicylic acid from the Chinese medical herb licorice and a lab-synthesized derivative bind to GAPDH more effectively than salicylic acid.
"A better understanding of how salicylic acid and its derivatives regulate the activities of GAPDH and HMGB1, coupled with the discovery of much more potent synthetic and natural derivatives of salicylic acid, provide great promise for the development of new and better salicylic acid-based treatments of a wide variety of prevalent, devastating diseases," Klessig said in the release.