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A Blueprint for Osteoporosis Treatments With Fewer Side Effects

Precise Imaging of the Molecular Conduit Could Inform Better Medications

An international team of researchers working at the Van Andel Research Institute (VARI), Grand Rapids, Michigan, has announced a significant advance that could inform the development of new medications for treatment of osteoporosis and cancer. The breakthrough involves imaging of the parathyroid hormone receptor-1 (PTH1R) at near-atomic resolution to better understand how it interacts with molecular messengers including the parathyroid hormone to regulate calcium levels in the blood. Co-corresponding author H. Eric Xu, PhD, a professor at VARI, remarked, “The understanding of how all of these molecules fit together has been a missing piece of the puzzle since the discovery of parathyroid hormone 80 years ago. It’s a big step forward that we hope will one day help people around the world.” The findings were published last week in the journal Science.

Osteoporosis affects some 200 million individuals worldwide, and this incidence is expected to spike with the advent of an aging population. Current medications are frequently resisted by sufferers due to rare, but severe side effects. The research additionally provides new insight in to G protein-coupled receptors (GPCRs), a family of signally proteins that are targeted by some 30% of today’s medications, and which have resisted structural determination via traditional x-ray crystallography techniques. The additional resolution provided by cryo-electron microscopy that was engaged in the present research enables the imaging of molecules like GPCRs that are embedded in the cell membrane.

Read about the study findings.

The journal abstract may be read here.

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