Nav: Home

From receptor structure to new osteoporosis drugs

November 19, 2018

Osteoporosis affects about 400,000 people in Switzerland, mostly women after menopause. It is often described as a silent disease, because bone loss usually occurs little by little over the years and without any symptoms. The body gradually absorbs calcium from the bones, which become brittle. This process is controlled via what is called the parathyroid hormone (PTH) and a closely related peptide - a protein fragment. They bind to the PTH-1 receptor, thereby telling the body to either release calcium from the bone or to build new bone.

An extremely difficult undertaking

A team led by Andreas Plückthun, professor at the Department of Biochemistry of the University of Zurich (UZH), has now been able to determine the three-dimensional structure of the PTH-1 receptor. The atomic structure can now serve as the blueprint for the future development of drugs. Such receptor-binding compounds may slow down, and perhaps even reverse, osteoporosis to some degree. Determining the structure of this receptor was an extremely tough undertaking, as cells only produce a very small amount of it, and it is also very unstable. "The directed evolution and protein engineering methods we have developed over the last few years were absolutely instrumental in making this possible," explains Andreas Plückthun.

Disadvantages of current treatment

One of the most effective current treatments for severe osteoporosis involves the use of substances that look like the natural hormone and its related peptide. "However, this treatment is extremely expensive. The substances have to be injected into the thigh or abdomen once a day, and the treatment also has significant side effects," says Christoph Klenk, co-author of the study. The scientists are convinced that thanks to the new insights into the mechanisms of the PTH-1 receptor, new drugs can be developed that don't have any of the previous disadvantages. "The receptor is like a lock, and the peptides are the keys that turn it," describes Plückthun. "Having the atomic 3D blueprint on a computer screen gives us an unprecedented level of insight into how the lock actually works."

Understanding a whole class of receptors

The PTH-1 receptor is a member of the family of G protein-coupled receptors. In particular, these include receptors that bind to other hormones, such as the ones involved in controlling diabetes. The work by the UZH scientists thus also sheds light on how the whole family of receptors works, as the PTH-1 receptor was examined at the highest level of detail for any of these receptors so far. This has enabled the scientists to describe similarities as well as differences to other class B receptors. "Having the blueprint of the lock doesn't give us a key yet, but now it's possible to build one," says Andreas Plückthun.
-end-


University of Zurich

Related Osteoporosis Articles:

New pharmaceutical target reverses osteoporosis in mice
Biomedical engineers at Duke University have discovered that an adenosine receptor called A2B can be pharmaceutically activated to reverse bone degradation caused by osteoporosis in mouse models of the disease.
A link between mitochondrial damage and osteoporosis
In healthy people, a tightly controlled process balances out the activity of osteoblasts, which build bone, and osteoclasts, which break it down.
Many stroke patients not screened for osteoporosis, despite known risks
Many stroke survivors have an increased risk of osteoporosis, falls or breaks when compared to healthy people.
Many postmenopausal women do not receive treatment for osteoporosis
The benefits of treating osteoporosis in postmenopausal women outweigh the perceived risks, according to a Clinical Practice Guideline issued today by the Endocrine Society.
A new 'atlas' of genetic influences on osteoporosis
A ground-breaking new study led by researchers from the Lady Davis Institute (LDI) at the Jewish General Hospital (JGH) has succeeded in compiling an atlas of genetic factors associated with estimated bone mineral density (BMD), one of the most clinically relevant factors in diagnosing osteoporosis.
New recommendations for the conduct of economic evaluations in osteoporosis
An expert working group has established recommendations for the design and conduct of economic evaluations in osteoporosis, as well as guidance for reporting these evaluations.
From receptor structure to new osteoporosis drugs
Researchers at the University of Zurich have determined the three-dimensional structure of a receptor that controls the release of calcium from bones.
How a Mediterranean diet could reduce osteoporosis
Eating a Mediterranean-type diet could reduce bone loss in people with osteoporosis -- according to new research from the University of East Anglia.
Osteoporosis drug may benefit heart health
The osteoporosis drug alendronate was linked with a reduced risk of cardiovascular death, heart attack, and stroke in a Journal of Bone and Mineral Research study of patients with hip fractures.
New treatment for osteoporosis provides better protection against fractures
A new treatment for osteoporosis provides major improvements in bone density and more effective protection against fractures than the current standard treatment.
More Osteoporosis News and Osteoporosis Current Events

Trending Science News

Current Coronavirus (COVID-19) News

Top Science Podcasts

We have hand picked the top science podcasts of 2020.
Now Playing: TED Radio Hour

Teaching For Better Humans 2.0
More than test scores or good grades–what do kids need for the future? This hour, TED speakers explore how to help children grow into better humans, both during and after this time of crisis. Guests include educators Richard Culatta and Liz Kleinrock, psychologist Thomas Curran, and writer Jacqueline Woodson.
Now Playing: Science for the People

#556 The Power of Friendship
It's 2020 and times are tough. Maybe some of us are learning about social distancing the hard way. Maybe we just are all a little anxious. No matter what, we could probably use a friend. But what is a friend, exactly? And why do we need them so much? This week host Bethany Brookshire speaks with Lydia Denworth, author of the new book "Friendship: The Evolution, Biology, and Extraordinary Power of Life's Fundamental Bond". This episode is hosted by Bethany Brookshire, science writer from Science News.
Now Playing: Radiolab

Space
One of the most consistent questions we get at the show is from parents who want to know which episodes are kid-friendly and which aren't. So today, we're releasing a separate feed, Radiolab for Kids. To kick it off, we're rerunning an all-time favorite episode: Space. In the 60's, space exploration was an American obsession. This hour, we chart the path from romance to increasing cynicism. We begin with Ann Druyan, widow of Carl Sagan, with a story about the Voyager expedition, true love, and a golden record that travels through space. And astrophysicist Neil de Grasse Tyson explains the Coepernican Principle, and just how insignificant we are. Support Radiolab today at Radiolab.org/donate.