18 January,Washington D.C
A team of researchers has discovered an anti-ageing protein, named after a Greek goddess, which may play an important role in the treatment of multiple diseases ranging from diabetes to cancers.
The findings indicated that the three-dimensional structure of one of the so-called Klotho proteins has a big role in the regulation of longevity and metabolism.
The Klotho family of two receptor proteins is located on the surface of cells of specific tissues.
The proteins bind to a family of hormones, designated endocrine Fibroblast Growth Factor (FGFs) that regulate critical metabolic processes in the liver, kidneys and brain, among other organs.
The researchers from Yale University used X-ray crystallography, a technique that provides high-resolution, three-dimensional views of these proteins.
They revealed, 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.
Senior author Joseph Schlessinger said, “Like insulin, FGF21 stimulates metabolism including glucose uptake”.
The senior researcher also added that “in animals and in some clinical trials of FGF21, it shows that you can increase burning of calories without changing food intake and we now understand how to improve the biological activity of FGF21.”
The authors also describe a new variant of FGF21 has 10 times higher potency and cellular activity.
Additionally, the 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 — may not be a coincidence.
Having untangled the structure of beta-Klotho, the researchers 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.
“The next step will be to make better hormones, make new potent blockers, do animal studies, and move forward,” Schlessinger said.
The research appears in the journal, called Nature.