Wonder acid: Fighting Alzheimer’s

Scientists are taking a closer look at the main breakdown product of aspirin, called salicylic acid, and its potential to treat Alzheimer’s and Parkinson’s. Salicylic acid binds to an enzyme called GAPDH which is believed to play a major role in such diseases. The acid stops the enzyme from moving into a cell’s nucleus, where it can trigger the cell’s death.

Daniel Klessig from the Boyce Thompson Institute and Cornell University, studied the actions of salicylic acid but in plants. Salicylic acid is the hormone for regulating plant immune systems. Studies have identified several targets in plants that are affected by salicylic acid and many of these targets have equivalents in humans.

Fighting cell death
In the new study in PLOS ONE, experts performed high-throughput screens to identify proteins in humans that bind to salicylic acid. GAPDH is a central enzyme in glucose metabolism but plays additional roles in the cell. Under oxidative stress — an excess of free radicals and other compounds — GAPDH is modified and then enters the nucleus of neurons, where it enhances protein turnover leading to cell death.

The anti-Parkinson’s drug deprenyl blocks GAPDH’s entry into the nucleus and the resulting cell death. Researchers found that salicylic acid also is effective at stopping GAPDH from moving into the nucleus, thus preventing cell death.

“GAPDH, long thought to function solely in glucose metabolism, is now known to participate in intracellular signalling,” says study co-author Solomon Snyder, professor of neuroscience at 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.”

Alternatives
Experts also found that a natural derivative of salicylic acid from the Chinese medical herb licorice and a lab-synthesised derivative bind to GAPDH more tightly than salicylic acid. Both are more effective than salicylic acid at blocking GAPDH’s movement into the nucleus.

Earlier this year, Klessig’s group identified another novel target of salicylic acid called HMGB1 which causes inflammation and is associated with several diseases, including arthritis, lupus and certain cancers.

Low levels of salicylic acid block pro-inflammatory activities, and salicylic acid derivatives are 70 times more potent than salicylic acid at inhibiting pro-inflammatory activities.

“A better understanding of how salicylic acid regulates the activities of GAPDH and HMGB1 provides great promise for new and better salicylic acid-based treatments of a wide variety of prevalent, devastating diseases,” says Klessig.

Source: www.futurity.org
 

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