Salicylic acid and its binding proteins at the crossroads of plant and human health

During the past several years, we have identified over two dozen plant SA-binding proteins (SABPs), primarily through biochemical methods including three high-throughput screens ( SA binding alters the biochemical and/or biological activities of these proteins. This work has been extended to humans, since the most widely used medicine aspirin (acetyl SA) is rapidly converted to SA after ingestion and SA has most of the same pharmacological activities of aspirin. Two novel targets of SA/aspirin have been identified across the animal and plant kingdoms. Together the two human SABPs are associated with most of the major human diseases, including heart attack, arthritis, cancers, and Alzheimer’s and Parkinson’s diseases.
One of the identified human SABPs is nuclear High Mobility Group Box1 (HMGB1). Extracellular HMGB1 is a damage-associated molecular pattern (DAMP), which activates immune and inflammatory responses. SA suppresses HMGB’s pro-inflammatory activities. A parallel study of the plant ortholog AtHMGB3 revealed that it also functions as a DAMP to activate plant immunity, which is inhibited by SA.
The second novel target in is Glyceraldehyde 3-Phosphate Dehydrogenase (GAPDH). In addition to its central role in glycolysis, GAPDH participates in several pathological processes including cell death associated with neurodegenerative diseases. SA suppresses this cell death. Some animal and plant viruses, such as human Hepatitis A, B, C Viruses and Tomato Bushy Stunt Virus (TBSV), usurp this host protein for their replication. SA binding to GAPDH inhibits TBSV replication. Synthetic and natural SA derivatives have been identified, which are 10-70 times more potent than SA at inhibiting HMGB1’s and GAPDH’s disease-associated activities, thereby providing proof-of-concept that better SA-based drugs can be obtained.

Invited Lecturer at National and International Meetings: 100+
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