The multidisciplinary team included researchers from the Virginia Commonwealth University School of Medicine, together with the Mount Sinai School of Medicine in New York and the University of Maryland School of Pharmacy in Baltimore. In an earlier, but related study, the Mount Sinai School of Medicine team had shown that two brain receptors, which bind the critical neurotransmitter signals serotonin and glutamate at the outside of the cell, form a complex in the areas of the brain that malfunction in schizophrenic patients.
The team has now developed a metric that may help determine the effectiveness of antipsychotic drugs and advance drug design. The present work fills an important gap in knowledge as previously researchers did not understand how this receptor complex was connected to the phenotype of schizophrenia.
The current study findings show that the connection between the complex of the two receptors and the schizophrenic phenotype is a defect in how the serotonin and glutamate signals get interpreted at the inside of the cell, a process referred to as signaling. Moreover, it shows how antipsychotic drugs used to treat patients work to correct such a defect in the brain.
“Not only have we learned how antipsychotics drugs are effective, but we have also found that the signaling through this receptor complex is critical to how these anti-psychotics work,” said the study’s principal investigator Diomedes E. Logothetis, Ph.D., an internationally recognized leader in the study of ion channels and cell signaling mechanisms and chair of the VCU School of Medicine’s Department of Physiology and Biophysics.
According to Logothetis, the most common cellular targets for drugs used in the clinic and by the pharmaceutical industry are G protein-coupled receptors, such as the ones that were examined in this study. Using cell and animal models, they found that the receptors signal very differently when they are together as a complex than when they are apart.
The metric developed by the team could be used to screen new drugs and determine their level of effectiveness, or be used to assess combination therapies - that is, putting two previously ineffective drugs together and making them more useful for some patients. Ultimately this work may translate to creating better antipsychotic drugs for patients.
“We can use the metric we developed to screen new drugs and determine their level of effectiveness,” Logothetis said. “We can also use the metric to assess what combinations of existing drugs will give us the ideal balance between the signaling through the two receptors of the complex.”
Logothetis said the hope is that by using this approach one day researchers will be able to develop a means by which high-throughput screening of drugs can be performed and they also will be able to develop more effective combinations of drugs that are able to help the third of schizophrenic patients who do not respond to current treatments.
Future studies will focus on further identifying the protein targets of the unique signaling pattern of this receptor complex and their link to schizophrenia.
The study was supported by grants from the National Institutes of Health.
EDITOR’S NOTE: A copy of the study is available for reporters by email request from the journal by contacting firstname.lastname@example.org.
About VCU and the VCU Medical Center: Virginia Commonwealth University is a major, urban public research university with national and international rankings in sponsored research. Located on two downtown campuses in Richmond, VCU enrolls more than 31,000 students in 216 certificate and degree programs in the arts, sciences and humanities. Sixty-nine of the programs are unique in Virginia, many of them crossing the disciplines of VCU’s 13 schools and one college. MCV Hospitals and the health sciences schools of Virginia Commonwealth University compose the VCU Medical Center, one of the nation’s leading academic medical centers. For more, see www.vcu.edu.
Sathya Achia Abraham | Newswise Science News
The importance of biodiversity in forests could increase due to climate change
17.11.2017 | Deutsches Zentrum für integrative Biodiversitätsforschung (iDiv) Halle-Jena-Leipzig
Win-win strategies for climate and food security
02.10.2017 | International Institute for Applied Systems Analysis (IIASA)
Heat from the friction of rocks caused by tidal forces could be the “engine” for the hydrothermal activity on Saturn's moon Enceladus. This presupposes that...
The WHO reports an estimated 429,000 malaria deaths each year. The disease mostly affects tropical and subtropical regions and in particular the African continent. The Fraunhofer Institute for Silicate Research ISC teamed up with the Fraunhofer Institute for Molecular Biology and Applied Ecology IME and the Institute of Tropical Medicine at the University of Tübingen for a new test method to detect malaria parasites in blood. The idea of the research project “NanoFRET” is to develop a highly sensitive and reliable rapid diagnostic test so that patient treatment can begin as early as possible.
Malaria is caused by parasites transmitted by mosquito bite. The most dangerous form of malaria is malaria tropica. Left untreated, it is fatal in most cases....
The formation of stars in distant galaxies is still largely unexplored. For the first time, astron-omers at the University of Geneva have now been able to closely observe a star system six billion light-years away. In doing so, they are confirming earlier simulations made by the University of Zurich. One special effect is made possible by the multiple reflections of images that run through the cosmos like a snake.
Today, astronomers have a pretty accurate idea of how stars were formed in the recent cosmic past. But do these laws also apply to older galaxies? For around a...
Just because someone is smart and well-motivated doesn't mean he or she can learn the visual skills needed to excel at tasks like matching fingerprints, interpreting medical X-rays, keeping track of aircraft on radar displays or forensic face matching.
That is the implication of a new study which shows for the first time that there is a broad range of differences in people's visual ability and that these...
Computer Tomography (CT) is a standard procedure in hospitals, but so far, the technology has not been suitable for imaging extremely small objects. In PNAS, a team from the Technical University of Munich (TUM) describes a Nano-CT device that creates three-dimensional x-ray images at resolutions up to 100 nanometers. The first test application: Together with colleagues from the University of Kassel and Helmholtz-Zentrum Geesthacht the researchers analyzed the locomotory system of a velvet worm.
During a CT analysis, the object under investigation is x-rayed and a detector measures the respective amount of radiation absorbed from various angles....
15.11.2017 | Event News
15.11.2017 | Event News
30.10.2017 | Event News
23.11.2017 | Information Technology
23.11.2017 | Physics and Astronomy
23.11.2017 | Life Sciences