In a recent study, researchers found that a component of aspirin binds to an enzyme called GAPDH.
This process is believed to play a major role in neurodegenerative diseases, including Alzheimer’s, Parkinson’s and Huntington’s diseases.
The study was conducted by the researchers at the Boyce Thompson Institute and John Hopkins University.
The study discovered that salicylic acid, the primary breakdown product of aspirin, binds to GAPDH, thereby stopping it from moving into a cell’s nucleus, where it can trigger the cell’s death.
It also suggests that derivatives of salicylic acid may hold promise for treating multiple neurodegenerative diseases.
Salicylic acid is the critical hormone for regulating the plant immune system.
Previous studies have identified several targets in plants that are affected by salicylic acid, and many of these targets have equivalents in humans.
In the current study, the researchers performed high-throughput screens to identify proteins in the human body that bind to salicylic acid.
GAPDH (Glyceraldehyde 3-Phosphate Dehydrogenase) is a central enzyme in glucose metabolism but plays additional roles in the cell.
Under oxidative stress, GAPDH is modified and then enters the nucleus of neurons, where it enhances protein turnover, leading to cell death.
oxidative stress is an excess of free radicals and other reactive compounds.
The anti-Parkinson’s drug deprenyl blocks GAPDH’s entry into the nucleus and the resulting cell death.
The researchers discovered that salicylic acid also is effective at stopping GAPDH from moving into the nucleus, thus preventing the cell from dying.
The team suggests that the enzyme GAPDH, long thought to function solely in glucose metabolism, is now known to participate in intracellular signaling.
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.
In addition, the team found that a natural derivative of salicylic acid from the Chinese medical herb licorice and a lab-synthesized derivative bind to GAPDH more tightly than salicylic acid.
Both are more effective than salicylic acid at blocking GAPDH’s movement into the nucleus and the resulting cell death.
Earlier this year, the team identified another novel target of salicylic acid called HMGB1 (High Mobility Group Box 1).
It causes inflammation and is associated with several diseases, including arthritis, lupus, sepsis, atherosclerosis and certain cancers.
The researchers found that low levels of salicylic acid block these pro-inflammatory activities, and the above mentioned salicylic acid derivatives are 40 to 70 times more potent than salicylic acid at inhibiting these pro-inflammatory activities.
The team believes their study provides a better understanding of how salicylic acid and its derivatives regulate the activities of GAPDH and HMGB1.
They also discovered much more potent synthetic and natural derivatives of salicylic acid.
All of the results provide great promise for the development of new and better salicylic acid-based treatments of a wide variety of prevalent, devastating diseases.
Senior author Daniel Klessig is a professor at Boyce Thompson Institute and Cornell University.
The study is published in the journal PLOS ONE.
The findings are confirmed by other studies.
In another study, researchers found that a low-dose aspirin regimen may represent a new avenue for reducing Alzheimer’s disease pathology.
The study is conducted in a mouse model of the disease.
The researchers show that this common over-the-counter drug could decrease amyloid plaque pathology in mice by stimulating lysosomes — the component of animal cells that help clear cellular debris.
The research adds to aspirin’s established uses for pain relief and for the treatment of cardiovascular diseases.
This finding is published in Journal of Neuroscience.
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Source: Society for Neuroscience, Boyce Thompson Institute for Plant Research