Brain study reveals promising new approach to treating depression

Researchers at the Wertheim UF Scripps Institute for Biomedical Innovation & Technology in the US have found that the inhibitory effect of glycine, a commonly occurring amino acid in the brain, could be a promising new therapeutic target for mood disorders such as major depression and anxiety.

This discovery could potentially accelerate the development of faster-acting medications for these conditions, which can be difficult to treat.

In a recent study published in the journal Science, the scientists explained that answering the question of how sensors on brain cells receive and transmit signals is key to understanding various processes such as vision, pain, memory, and behaviour.

"It's amazing how basic science goes. Fifteen years ago, we discovered a binding partner for proteins we were interested in, which led us to this new receptor," said Kirill Martemyanov, corresponding author of the study.

In 2018, the researchers discovered that mice lacking the GPR158 gene exhibited resilience to chronic stress, providing strong evidence that GPR158 could serve as a therapeutic target. However, the question of what sent the signal remained unanswered.

In 2021, the team solved the structure of GPR158 and found that the receptor resembled a microscopic clamp with a compartment, similar to something found in bacteria rather than human cells.

"We were barking up the completely wrong tree before we saw the structure," said Martemyanov, who chairs the neuroscience department at the institute.

"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," he said.

Additionally, the team discovered that the signalling molecule associated with GPR158 was not an activator, but rather an inhibitor in the cells.

In other words, the researchers explained that the active part of GPR158 was connected to a partnering molecule that slowed down cellular activity, rather than speeding it up, when glycine was bound to it.

According to Thibaut Laboute, the first author of the study, G protein Coupled Receptors, such as GPR158, typically bind G proteins. However, in this case, the receptor was binding to an RGS protein, which has the opposite effect of activation.

Glycine is marketed as a nutritional supplement with claims of improving mood. As a fundamental component of proteins, glycine impacts various cell types, often in intricate ways. But while it can transmit inhibitory signals in certain cells, it can also convey excitatory signals in others. Martemyanov noted that there is a pressing need for new and improved medication options.

(With inputs from PTI)