The Klotho family of two receptor proteins decide the number of days that you can live.
Klotho proteins play an important role in the regulation of longevity and metabolism. In a recent Yale-led study, the research team revealed the three-dimensional structure of one of these proteins, beta-Klotho, illuminating its intricate mechanism and therapeutic potential.
The study findings, could have implications for therapies developed to treat a wide range of medical conditions, including diabetes, obesity, and certain cancers, the research team said.
Striking Features of The Protein
- First, beta-Klotho is the primary receptor that binds to FGF21, a key hormone produced upon starvation.
- When bound to beta-Klotho, FGF21 stimulates insulin sensitivity and glucose metabolism, causing weight loss.
- This new understanding of beta-Klotho and FGF21 can guide the development of therapies for conditions such as type 2 diabetes in obese patients, the researchers said.
Additionally, the research team presented evidence of how a structurally-related enzyme, glycosidase, which breaks down sugars, evolved into a receptor for a hormone that lowers blood sugar -- which may not be a coincidence, Schlessinger added.
Having untangled the structure of beta-Klotho, Schlessinger and his colleagues have a platform for exploring potential therapies for multiple diseases. By developing drugs that enhance the pathway, he said, researchers can target diabetes and obesity. Conversely, using agents that block the pathway, they hope to explore therapies for conditions such as liver cancer and bone diseases, among others.
"The next step will be to make better hormones, make new potent blockers, do animal studies, and move forward," Schlessinger said.