Dormant no more: Brain protein’s hidden role may reshape psychiatric and neurological treatments

In a new research report, scientists at Johns Hopkins Medicine say they have identified a potential target for drugs that could dial up or down the activity of certain brain proteins in efforts to treat psychiatric disorders, such as anxiety and schizophrenia, and a neurological condition that affects movement.

The proteins, called delta-type ionotropic glutamate receptors, or GluDs, have long been understood to play a major role in signaling between neurons. Mutations in GluD proteins are thought to drive psychiatric conditions, including anxiety and schizophrenia, the scientists say. Yet, scientists had few clues as to how GluDs function, hampering the ability to find treatments to regulate them.

“This class of protein has long been thought to be sitting dormant in the brain,” says Edward Twomey, Ph.D., assistant professor of biophysics and biophysical chemistry at the Johns Hopkins University School of Medicine. “Our findings indicate they are very much active and offer a potential channel to develop new therapies.”

A report on the study’s findings was published Sept. 16 in Nature.

Using cryo-electron microscopy, a highly specialized microscope, Twomey and his team of scientists characterized the form and function of GluDs. Twomey says an ion channel in the center of GluDs houses charged particles that help GluDs bind to neurotransmitters (electrical signals that allow brain cells to communicate with one another).

“This process is fundamental for the formation of synapses, the connection point where cells communicate,” says Twomey.

Morph between hGluD2R710W-apo-closed and hGluD2R710W-apo-leak. Credit: Nature (2025). DOI: 10.1038/s41586-025-09610-xThe finding could help speed up drug development and discovery in conditions such as cerebellar ataxia, a movement and balance disorder that could result from stroke, head trauma, brain tumors and certain neurodegenerative conditions. In this disorder, which can also cause memory problems, GluDs become “super-active” even in the absence of electrical signaling. To potentially treat cerebellar ataxia, Twomey says scientists could identify a drug that blocks the hyperactive state in GluDs.

In schizophrenia, where GluDs are known to be less active, Twomey says drugs could potentially dial-up GluD activity.

The findings could also apply to aging and memory loss, in which drugs targeting GluDs could potentially preserve the function of synapses, which play a significant role in the formation of thought and memory.

“Because GluDs directly regulate synapses, we could potentially develop a targeted drug for any condition where synapses malfunction,” Twomey says.

Up next, Twomey says he is looking to partner with pharmaceutical companies to develop this therapeutic target. In addition, his team is investigating mutations of GluDs directly implicated in schizophrenia, anxiety and other psychiatric disorders to better understand disease progression and develop more precise therapeutics.

Additional scientists who contributed to this work are Haobo Wang, Fairine Ahmed, Jeffrey Khau and Anish Kumar Mondal from Johns Hopkins.

The Johns Hopkins University has filed a patent for the techniques used to record electrical currents from GluDs.

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