Ingredient in aspirin combined with popular diabetes drug can turn off faulty protein that plays a key role in inflammatory diseases, such as rheumatoid arthritis.
The widely used diabetes drug metformin and the main ingredient found in aspirin can together control a new biochemical pathway thought to play a key role in some inflammatory diseases.
Janus kinase (JAK) proteins play a role in the control of inflammation in certain tissues, acting as gatekeepers at the surface of cells, reacting to immune system signals, and transmitting the messages inside the cell.
Unfortunately, JAK proteins can also carry a mutation that causes them to be permanently turned on and overactive. However, in a new study published in Science Signaling, researchers identified another protein called AMP-activated protein kinase (AMPK) that has the ability to turn JAK1 off even when it’s faulty.
“While our studies are at the very early stage, we’ve identified a new biochemical process that suggests certain anti-diabetic drugs could potentially be repurposed to treat diseases caused by activated Janus kinase proteins,” said lead researcher Tim Palmer.
Researchers identified that AMPK is able to do this by chemically altering 2 key amino acids in the JAK1 protein through the process phosphorylation. Furthermore, they were able to demonstrate that metformin and salicylate — the main ingredient in aspirin – could activate AMPK to turn of JAK1.
“We found this AMPK pathway is able to profoundly inhibit JAK signaling and it seems to work in a way that other drugs that target the JAK proteins do not,” Palmer said.
The findings suggest that this approach could be used to turn off other Janus kinase proteins that have been found to be active in other diseases, the authors noted.
“Although it is still early in our work, our findings suggest we can design future therapies for those disorders that target this pathway,” said study co-author Ian Salt. “Indeed, as AMPK is known to be stimulated by a number of existing anti-diabetic drugs, they should be investigated as potential drugs to treat those disorders.”