Targeting double-stranded RNA dependent protein kinase could treat inflammation

Researchers at The Feinstein Institute for Medical Research have discovered that inflammation could be treated by targeting a molecule called the double-stranded RNA dependent protein kinase (PKR). These findings are published in the July issue of Nature.

"Inflammation is necessary for maintaining good health, but when unchecked, it can play a part in a wide array of human diseases, such as arthritis, colitis and sepsis," said Scott Somers, Ph.D., who oversees inflammation grants at the National Institutes of Health (NIH), which partly supported the study. "By identifying a protein that controls a single aspect of inflammation, this work offers a new way to target the harmful effects of chronic inflammation while preserving the body's overall protective mechanisms."

The inflammasome is protein complex in cells that provides immediate defense against infection. It is found in all classes of plant and animal life and is fundamental in regulating the activation process of inflammation. Without inflammation, wounds and infections would never heal. However, persistent and constant inflammation can damage tissue and organs, and lead to diseases such as sepsis, rheumatoid arthritis, and even cancer. Therefore, it is important to identify ways in which persistent and constant inflammation can be halted.

In studying inflammation, Feinstein Institute researchers discovered that double-stranded RNA dependent protein kinase (PKR), a molecule not previously linked to the inflammasome, plays a critical role in inflammasome activation. Further, they found that targeting this molecule could treat inflammation.

"We are particularly interested in this discovery because it provides a new way to make novel drugs to treat obesity, Alzheimer's disease, diabetes, atherosclerosis and a host of other diseases." Noted Kevin J. Tracey, M.D., president of the Feinstein Institute, and lead investigator of the study, which was funded by the NIH institutes the National Institute of General Medical Sciences and the National Institute of Diabetes and Digestive and Kidney Diseases – the grant numbers are GM062508 and DK052539.