New target explored for psychiatric drug development

In a surprising discovery, neuroscientists have found that a breakdown product of cholesterol in the brain may be a target for developing new drugs to treat schizophrenia and other mental illnesses.

Although the research is in its early stages, the finding comes at a crucial time. Most existing drugs to treat schizophrenia work in similar ways, targeting dopamine receptors in the brain, but many patients don’t respond well to the medications or can’t tolerate the side effects.

The investigators, from Washington University School of Medicine in St. Louis, SAGE Therapeutics and Weill Cornell Medical College, report in The Journal of Neuroscience that a molecule known as an oxysterol helps control a different type receptor in the brain that is key in cognitive function.

Because the naturally occurring oxysterol molecule interacts with receptors not normally associated with medications used to treat serious psychiatric illnesses, the researchers believe it could be useful in the development of new types of antipsychotic drugs.

The molecule, called 24(S)-hydroxycholesterol, targets NMDA receptors in the brain, which are important in processes thought to be the biological underpinnings of learning and memory.

Although most existing antipsychotic drugs instead target dopamine receptors, drugs that block NMDA receptor function—such as the anesthetic ketamine and the street drug PCP—can produce psychotic symptoms or relieve depression, depending on the dosage. The researchers believe that molecules that enhance activity in NMDA receptors may help control psychotic symptoms and limit the learning and memory problems that accompany illnesses such as schizophrenia.

1 Like