Proteins related to schizophrenia discovered

BARCELONA.— An international study, published in the journal “Nature Communications”, identified the role of two proteins in modulating the symptoms of schizophrenia, what opens the door to new personalized treatments.

The study was carried out by the Research Institute of Barcelona Sea Hospital, together with the Neuropsychopharmacology Group of the University of the Basque Country (UPV), the Mental Health Cyber ​​​​(Cibersam), the University of Montreal (Canada) and the Swiss experimental and computational pharmacology company InterAx Biotech.

The project is focused on people with schizophrenia who present different types of symptoms, such as delusions, hallucinations, cognitive deficits —with impairment of the memory or language— y depressive symptoms.

This disparity in symptoms is a challenge when applying current treatments, which are largely directed at a single specific therapeutic target, the serotonin type 2A receptor.

Thus, with these treatments in force, it is not possible to selectively affect the symptoms that each patient has, which causes metabolic or motor side effects, which sometimes lead patients to stop taking the medication.

Key in modulation

The New research has made it possible to determine the role of G proteinsspecifically two types of them that have a vital function in the modulation of cell response in schizophrenia.

“These proteins are coupled to the same receptor, but they do not act in the same way, causing different reactions in the cells,” explained the doctor. Jana Selent, one of the lead authors of the study and a researcher at Hospital del Mar.

These reactions provide “very valuable information for future studies that allow the development of drugs for treating schizophrenia on an individual basis, adapted to the symptoms of each patient,” he added.

To reach these conclusions, the researchers selected four compounds that were first studied in cells where it was shown that, by binding to the serotonin type 2A receptor, they triggered responses in different types of G proteins.

Treatment in humans

These results were transferred to analysis in samples of human brain tissue from the collection of the Neuropsychopharmacology Group of the UPV.

In them it was possible to verify the way in which The compounds had very different activity towards G proteins; some turned them on, but others turned them off.

It was also tested in mouse models designed for simulate the symptoms of schizophrenia and the researchers observed that these compounds had specific behavioral effects depending on what G protein activated.

Thus, using pharmacological and genetic techniques in mice, it was found that one of these G proteins is involved in symptoms related to psychosis and another type of G protein is involved in cognitive deficits.

Although the compounds used in the study are not yet drugs for human use, the researchers believe that this work shows a path for the chemical design of future drugs that address more specific pathways for the treatment of schizophrenia, avoiding pathways associated with side effects.

“The possibility of inhibiting the coupling of the serotonin 2A receptor to certain G proteins has been proposed for the design of a new type of drugs, called inverse agonists, as potential tools against psychotic conditions,” said the UPV researcher, Rebecca Diez-Alarcia.