A new study, published by PLOS ONE, has discovered that a breakdown product of aspirin interacts with one of the enzymes that is responsible for degenerative diseases such as Parkinson’s, Alzheimer’s, and Huntington’s diseases.
The team discovered that salicylic acid, the primary component of aspirin, binds to the enzyme GAPDH (Glyceraldehyde 3-Phosphate Dehydrogenase), which is thought to be the cause of brain cell death in degenerative diseases. The study has shown that two synthetic versions of salicylic acid and two compounds extracted from the licorice plant, where it naturally occurs, are very effective at inhibiting GAPDH.
GAPDH is used by our body to regulate sugar absorption and use, but it has other functions as well. If a person has an excess of free radicals – known as oxidative stress – GAPDH mutates and enters the nucleus of neurons leading to cell death.
By binding itself to GAPDH, salicylic acid stops the enzyme from entering brain cells, thus avoiding cell deaths. Other drugs, such as deprenyl, act on GAPDH and they are used to prevent degenerative diseases.
"The enzyme GAPDH, long thought to function solely in glucose metabolism, is now known to participate in intracellular signaling," coauthor Solomon Snyder, professor of neuroscience at Johns Hopkins University in Baltimore, said in a statement. "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 health benefits of salicylic acid has been known since ancient times, and it has been used to reduce fevers and provide pain relief. Before we could synthesize it in the lab, patients had to chew on the bark of willow trees, which is rich in salicylic acid.
In the last decade, there have been many studies interested in understanding the impact of aspirin on heart disease and cancer, with promising results, and larger studies are currently in the works. Salicylic acid has been shown to also stop HMGB1 (High Mobility Group Box 1) proteins, which cause inflammation by the same team who discovered the GAPDH inhibition mechanism. HMGB1 is associated with diseases such as arthritis, lupus, and sepsis.
Professor Daniel Klessig, senior author of the research, added: "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."
