From Medical Xpress:
Experiments confirmed the molecule p11 (green) increases the receptor mGluR5’s (red) presence on a cell’s surface. This change amplifies sensitivity to certain signals–including those that promote depression–among certain neurons. The new antidepressants appear to interfere with this process. Credit: Laboratory of Molecular and Cellular Neuroscience at The Rockefeller University/Molecular Psychiatry
A new class of drugs under development to treat depression has shown some success by targeting brain cells’ ability to respond to the chemical messenger glutamate. But the mechanism by which these experimental therapies work has remained unknown.
The recent discovery, by a Rockefeller University-led team, of a molecular amplification system helps explain how the drugs alter brain signaling in particular neurons, and so produce an antidepressant effect. The results, published September 15 in Molecular Psychiatry, center on a signal receptor known as mGluR5 found on neurons.
“Our experiments suggest that mGluR5 amplifies the cellular response to a chemical signal, and that by blocking mGlur5 receptors in inhibitory neurons involved in depression, these new therapies can achieve an antidepressant effect,” says senior author Paul Greengard, Vincent Astor Professor and head of the Laboratory of Molecular and Cellular Neuroscience. “Since mGluR5 is considered a target for treating a variety of neurological disorders, including Parkinson’s disease and Fragile X Syndrome, our research may have implications for therapies for diseases beyond depression.”
The path to mGluR5 began with the molecule p11. In 2006, Greengard’s lab and their colleagues linked decreased levels of p11, which increases neurons’ sensitivity to the chemical messenger…