A new study has discovered that a compound used in aspirin binds to the enzyme GAPDH to halt the accumulative cell death that occurs in a range of neurodegenerative diseases, including Alzheimer's, Parkinson’s, and Huntington's diseases.
The news comes just months after the same team discovered that the multi-tasking aspirin ingredient - salicylic acid - targets a protein coding gene called HMGB1 that’s associated with a range of diseases such as arthritis, lupus, sepsis, and different types of cancer. In other words, the world’s hardest working painkiller now offers up the potential for all kinds of new treatments that address the worst effects of inflammation and oxidative stress.
"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," said lead researcher Daniel Klessig from Cornell University.
GAPDH (Glyceraldehyde 3-Phosphate Dehydrogenase) is primarily responsible for regulating how the body metabolises glucose, but Klessig and his team discovered that it also appears to play a number of different roles within the cell. Klessig has spent years observing how salicylic acid - the primary breakdown product of aspirin - regulates immune systems in plants, but decided to test it out on a bunch of human proteins to see which ones would respond.
The researchers discovered that when neurons in the brain experience oxidative stress - when the balance between the production of reactive oxygen species (free radicals) and antioxidant defences is thrown out of whack - GAPDH moves into the nucleus to increase protein turnover, and this then leads to cell death.
But when they tested the effects of salicylic acid on GAPDH, they watched as the two became bound together. This meant GAPDH could no longer pass into the nucleus of brain's neurons.
"The enzyme GAPDH, long thought to function solely in glucose metabolism, is now known to participate in intracellular signalling," said one of the team, Solomon Snyder from Johns Hopkins University. "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."
The team is now continuing their investigation into the potential of salicylic acid as a wide-ranging treatment option. They say a derivative of salicylic acid that can be extracted from a variety of Chinese liquorice plant and a synthetic version both appear to bind more tightly to GAPDH than the pure version, so that's where they’re going to be focussing their future research efforts.
The results have been published in PLOS ONE.