Will aspirin prevent the development of neurodegenerative diseases?

Researchers at the Boyce Thompson Institute, part of Cornell University, and Johns Hopkins University have demonstrated that the product of aspirin metabolism – salicylic acid – binds to the enzyme glyceraldehyde-3-phosphate dehydrogenase (GAPDH), which, according to modern ideas, plays a major role in the development of neurodegenerative diseases, including Alzheimer's, Parkinson's and Huntington's diseases.

The head of the study, Professor Daniel Klessig, has been studying the effect of salicylic acid for many years, but his work was mainly devoted to plants. Salicylic acid is a critical hormone that regulates the immune system of plants. Earlier studies identified several salicylic acid targets in plant cells, many of which have equivalents in human cells.

In the new work, the authors conducted a high-performance screening to identify proteins of the human body that bind to salicylic acid.

The enzyme glyceraldehyde-3-phosphate dehydrogenase performs various functions in the cell; among other things, it is the main enzyme in glucose metabolism. Under conditions of oxidative stress – an excess of free radicals and other active compounds – glyceraldehyde-3-phosphate dehydrogenase undergoes modifications and penetrates into the nuclei of neurons, where it accelerates protein metabolism, which ultimately leads to cell death.

Deprenil, a drug used to treat Parkinson's disease, blocks the penetration of glyceraldehyde-3-phosphate dehydrogenase into the nuclei and subsequent cell death. The authors found that salicylic acid has a similar effect.

Moreover, they demonstrated that amorphrutins B1 and FN2, natural derivatives of salicylic acid contained in licorice (licorice), a plant widely used in phytotherapy, bind more strongly than deprenyl to glyceraldehyde–3-phosphate dehydrogenase, more effectively blocking the movement of the enzyme into the nucleus and the associated cell death.

Earlier this year, the authors identified another previously unknown target of salicylic acid, known as High Mobility Group Box1 (HMGB1) – a box-1 group (proteins) with high mobility, causing inflammation, as well as associated diseases, including arthritis, systemic lupus erythematosus, sepsis, atherosclerosis and some types cancer. Low concentrations of salicylic acid block this pro-inflammatory effect, and the effectiveness of the above-mentioned amorphrutins in this respect is 30-40 times higher than the effectiveness of salicylic acid itself.

The authors note that a better understanding of the mechanisms by which salicylic acid and its derivatives regulate the activity of glyceraldehyde-3-phosphate dehydrogenase and HMGB1, combined with the discovery of significantly more active derivatives of salicylic acid, opens up new prospects in the treatment of many common diseases.

Article by Hyong Woo Choi et al. Human GAPDH Is a Target of Aspirin's Primary Metabolite Salicylic Acid and Its Derivatives published in the journal PLOS ONE.

Evgeniya Ryabtseva

Portal "Eternal youth" http://vechnayamolodost.ru