Aspirin: a drug of many talents. Could it be used to prevent neurodegenerative diseases?
Plants have been used for healing throughout history. Plant and herb-based medicine is still a primary form of treatment worldwide.
Around 50% of the pharmaceuticals developed over the past 20 years and approved by the US Food and Drug Administration (FDA) are either natural products or synthetic derivatives of natural products, mainly derived from plants.
Salicylic acid (SA) and its derivatives are a prime example. SA is the critical hormone for regulating the plant immune system. It is also the primary breakdown product of acetyl SA or aspirin. SA and its derivatives have been used for thousands of years to reduce pain, fever, and inflammation.
Senior author Daniel Klessig, a professor at Boyce Thompson Institute - Cornell University in Ithaca, NY, has studied the actions of SA for a long time, mostly focusing on plants.
Several targets in plants that are affected by SA have been identified in previous studies; many of these targets have equivalents in humans.
Role for aspirin in Alzheimer's and Parkinson's?
Now it seems that SA's impressive repertoire could expand to include Alzheimer's, Parkinson's and Huntington's disease; one of its components has been found to bind to an enzyme called Glyceraldehyde 3-Phosphate Dehydrogenase (GAPDH), a culprit in these diseases.
GAPDH is a central enzyme in glucose metabolism but performs additional roles within the cell such as signaling.
Oxidative stress, which results from a lack of oxygen being delivered to the brain, is believed to contribute to these diseases. It leads to an excess of free radicals and other reactive compounds.
In these conditions, GAPDH is modified and enters the nucleus of neurons where it enhances protein turnover, leading to cell death.
The anti-Parkinson's drug deprenyl works by preventing GAPHD from entering into the nucleus.
Salicylic acid prevents GAPDH from entering nucleus
Researchers at the Boyce Thompson Institute and John Hopkins University - in Baltimore, MD - performed high-throughput screens to identify proteins in the human body that bind to SA.
They found that SA can bind to GAPDH and stop it from moving into the nucleus. They also found two other substances that bind more tightly to GAPDH than salicylic acid, in turn blocking GAPDH's movement into the nucleus and the resulting cell death more effectively. One is a natural derivative of salicylic acid from licorice, the other is a laboratory-synthesized derivative.
Earlier this year, Klessig's group identified another novel target of SA called High Mobility Group Box 1 (HMGB1), a protein that causes inflammation and is associated with several diseases, including arthritis, lupus, sepsis, atherosclerosis and certain cancers.
Low levels of SA block these pro-inflammatory activities, and the two other salicylic acid derivatives are 40-70 times more potent than salicylic acid at inhibiting them.
"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."
Medical News Today recently reported on the benefits and risks of aspirin.