Aspirin Targets Key Proteins In Alzheimer's, Parkinson's, Hungtinton's Disease

A study from the Boyce Thompson Institute for Plant Research found that an aspirin component binds to an enzyme that plays a major role in several neurodegenerative diseases, including Alzheimer's, Huntington's, and Parkinson's diseases. The enzyme, called GAPDH, moves into cells nuclei, eventually causing cell death for those who suffer from these diseases.

The team, headed by Daniel Klessig, a professor at Cornell University, found that aspirin's primary breakdown product, salicylic acid, binds to GAPDH and prevents it from entering the nucleus of the cell. The study also suggested that salicylic acid derivatives may provide a way to treat multiple neurodegenerative diseases. Salicylic acid is a main hormone in regulating plant's immune systems, where Klessig has studied its actions for many years.

A few studies have previously identified targets of salicylic acid in plants, many of which have human equivalents that had not been officially identified as pairable with the acid.

The researchers took part in high-throughput screens in order to identify proteins in the human body that salicylic acid will bind to. Normally, GAPDH plays a role in glucose metabolism, but under oxidative stress, also known as an excess of reactive compounds, GAPDH modifies and enters the nucleus, where it eventually leads to cell death by enhancing protein turnover.

Deprenyl, an anti-Parkinson's drug, blocks GAPDH's entry into the nucleus, which in turn blocks cell death. During the study, the researchers found that salicylic acid has the same effect.

"The enzyme GAPDH, long thought to function solely in glucose metabolism, is now known to participate in intracellular signaling," Solomon Snyder, a Johns Hopkins University professor of neuroscience, said in a news release. "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 also found that two derivatives of salicylic acid, a natural one from the Chinese medical herb licorice and a lab-snythesized one, caused an even tighter binding to GAPDH than salicylic acid itself. Klessig's team also found that HMGB1 can be blocked with low levels of salicylic acid and its derivatives. HMGB1 is another target of salicylic acid that causes inflammation and is associated with arthritis, lupus, sepsis, and atherosclerosis.

"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," Klessig said.

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