Discovery opens door to new depression treatmants

Discovery opens door to new depression treatments

By Stacey DeLoye

A common amino acid, glycine, can deliver a “slow-down” signal to the brain, likely influencing major depression, anxiety and other mood disorders in some people, scientists at The Herbert Wertheim UF Scripps Institute for Biomedical Innovation & Technology reported in Science in late March.

The discovery improves understanding of the biological causes of major depression and could accelerate efforts to develop faster-acting medications for such hard-to-treat mood disorders, said neuroscientist Kirill Martemyanov, Ph.D., who led the study.

“There are limited medications for people with depression,” said Martemyanov, who chairs the institute’s neuroscience department. “Most of them take weeks before they kick in, if they do at all.”

Major depression is among the world’s most urgent health needs. Its numbers have surged in recent years, especially among young adults. As depression’s numbers have climbed, its economic burden has been estimated at $326 billion a year in the U.S.

Martemyanov said his team spent many years working toward the discovery. They didn’t set out to find a cause, much less a possible treatment route for depression. Instead, they asked a basic question: How do sensors on brain cells receive and transmit signals into the cells, and then change the cells’ activity? Therein lay the key to understanding vision, pain, memory, behavior and possibly more, Martemyanov suspected.

In 2018 the Martemyanov team found the new receptor was involved in stress induced depression. If mice lacked the gene for the receptor, called GPR158, they proved surprisingly resilient to chronic stress.

That offered strong evidence that GPR158 could be a therapeutic target, he said. But what sent the signal?

A breakthrough came in 2021, when his team solved the structure of GPR158. What they saw surprised them. The GPR158 receptor looked like a microscopic clamp with a compartment — akin to something they had seen in bacteria, not human cells.

“We were barking up the completely wrong tree before we saw the structure,” Martemyanov said. “We said, ‘Wow, that’s an amino acid receptor.’ There are only 20,
so we screened them right away and only one fit perfectly. That was it. It was glycine.”

Glycine is sold as a nutritional supplement billed as improving mood. It is a basic building block of proteins and affects many different cell types, sometimes in complex ways. Some studies have linked glycine to the growth of invasive prostate cancer.