The Same Key Protein Linked To Depression, Obesity and Chronic Pain

protein

Researchers have for many years established that one key protein, called “FK506-binding protein 51″ or FKBP51, and its role in leading to the development of major depression, obesity, and chronic pain. However, targeting this protein for therapeutic purposes has been really difficult to achieve. This is because this protein could not be targeted without affecting neighboring protein which is due to the fact that the protein is expressed in multiple sites within the body which thus makes targeting really difficult. The protein is expressed in places such as the brain, skeletal muscle tissue and fat. Hence, interaction with the protein will show potential for multiple effects. For instance, the protein can inhibit glucose uptake in various muscle cells and tissues and the browning of fat. Hence, the body stores fat instead of burning it. It also affects stress responses. So, Hausch and co-workers discovered that blocking this protein could be the key to developing drugs to treat a variety of conditions.

Recently, researchers were able to develop a highly selective compound that can effectively block and interact with the FKBP51 in mice. The result is a relief from chronic pain as well as an improvement in weight gain and mood. The researchers were also able to discover that the compound could also have applications in alcoholism and brain cancer. One of the researchers, Felix Hausch, who is also the project’s principal investigator at the Technical University of Darmstadt, started the project when studies were published linking the protein to depression reported that, “I was intrigued by the peculiar regulatory role it seemed to play in cells,” he went further, “And there was a known natural product that could serve as a starting point. Collectively, this looked like an interesting protein to work on.” The major issue with the protein, FKBP51, is its nearly perfect structural similarity to FKBP52.

These two proteins are very similar structurally, although they perform different functions in cells. In fact, they perform opposing functions in cells. Hence, selectivity and specificity between these two proteins is quite crucial, but this is hard to achieve owing to the near perfect structural similarity between the proteins. The researchers were able to discover that FKBP51 can change its shape in a way that FKBP52 can’t, and this allowed the development of highly selective inhibitors. Thanks to the power of Nuclear Magnetic Resonance.

The researchers were able to utilize the power of nuclear magnetic resonance techniques to detect a previously hidden binding site in FKBP51. The scientists went further that other researchers working on other projects could use similar technique which they used to identify similar “cryptic” binding sites in challenging drug targets in the future.

It is hoped that the results of this research work and advances in this project would enable the development FKBP51 inhibitors which could be used in cancer treatment, when patients’ tumors mutate beyond current drugs’ capacity to treat them. It also hoped that advances in spectrometry techniques will allow for efficient molecular structure identification and purification that will enable the adequate structural elucidation of diverse range of molecular targets.