Component of aspirin found to block cell death associated with neurodegenerative diseases
01 Dec 2015
A component of aspirin could block cell death associated with neurodegenerative diseases like Alzheimer's, Parkinson's and Huntington's disease, a new study has found.
Aspirin binds to an enzyme called GAPDH, which is said play a role in neurodegenerative diseases.
"The enzyme GAPDH, long thought to function solely in glucose metabolism, is now known to participate in intra-cellular signaling," said study co-author Solomon Snyder, professor of neuroscience at Johns Hopkins University in Baltimore.
"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," he noted.
Salicylic acid is the primary breakdown product of aspirin.
"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," said Daniel Klessig a professor at Boyce Thompson Institute and Cornell University.
Salicylic acid stops the enzyme from moving into the cell's nucleus, where it could trigger the cell's death. According to the study, published in the journal PLOS ONE, derivatives of salicylic acid might hold promise for treating multiple neurodegenerative diseases. Klessig, had studied the actions of salicylic acid for many years, but mostly in plants.
Salicylic acid is the critical hormone for regulation of the plant immune system, and in the new study, the researchers performed high-throughput screens to identify proteins in the human body that bound to salicylic acid.
GAPDH undergoes modification under oxidative stress -an excess of free radicals and other reactive compounds. It then enters the nucleus of neurons, where it enhances protein turnover, leading to cell death. The anti-Parkinson's drug deprenyl does not allow GAPDH to enter the nucleus and prevents cell death.
The researchers found that salicylic acid could also effectively block GAPDH entry into the cell nucleus, thus preventing the cell from dying.
