Potential new enzyme inhibition to treat mental depression

The study just appeared in Molecular Psychiatry. During the past decade there has been increasing interest in studying the effects of oxidative stress on the central nervous system –– including how reactive oxygen species (ROS) formation might play a role in causing or modifying psychiatric disorders.


Potential new enzyme inhibition to treat mental depression

Brain enzyme inhibition is shown to alleviate depressive symptoms faster than traditional treatment in studies in mice

By Amy Wallace

March 21, 2017


A new study in mice found a potential new treatment for depression that is faster and more effective than traditional treatments.

March 21 (UPI) — Researchers at the University of California at San Diego School of Medicine have identified a potential new, faster treatment for depression.

Standard treatment for depression includes use of antidepressants, which often take days to build up in a person’s system before they are effective. Some patients even need to use more than one type of antidepressant to encounter positive results.

A new study from the University of California at San Diego School of Medicine has found that inhibiting the Glyoxalase-1, or GLO1, enzyme in mice relieves symptoms of depression and worked significantly faster than Prozac, a selective serotonin reuptake inhibitor.

Why was inhibition of GLO1 even considered in studies of mental depression in animal experiments? GLO1 is a ubiquitous cellular enzyme that detoxifies methylglyoxal, a cytotoxic byproduct of glycolysis that induces protein modification glycation end-products, oxidative stress, and apoptosis (programmed cell death). The concentration of methylglyoxal is elevated under high-glucose conditions such as diabetes, and therefore GLO1 activity and methylglyoxal have been implicated in the pathogenesis of diabetic complications. Studies have recently linked GLO1 to numerous behavioral phenotypes –– including psychiatric diseases (anxiety, depression, schizophrenia, and autism) and pain.

“Depression affects at least one in six of us at some point in our lifetime, and better treatments are urgently needed,” Abraham Palmer, professor of psychiatry and vice chair for basic research at the San Diego School of Medicine, said in a press release. “A better understanding of the molecular and cellular underpinnings of depression will help us find new ways to inhibit or counteract its onset and severity.”

The enzyme GLO1 typically removes degradation byproducts produced when cells generate energy, whereas inhibiting GLO1 also increases the activity of certain neurons in a beneficial way.

Researchers tested several different antidepressants and compared responses in mice that were untreated, mice treated by inhibiting GLO1 and mice treated with Prozac.

The study showed inhibiting the GLO1 enzyme decreased depression-like symptoms in five days–– compared to the 14 days it tokes for Prozac to reduce symptoms.

The method has only been tested in mice and will take several years before it can be tested in humans, but researchers say the GLO1 provides a promising target for future therapies.

“There are currently no approved fast-acting antidepressants, so finding something like this is unusual,” said Stephanie Dulawa, an associate professor of psychiatry at UC San Diego.

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