New target receptor for treating depression GPR158

Researchers from the Scripps Research Institute find a new target receptor called GPR158 for treating depression. Their research shows that individuals with high levels of above receptor may be more susceptible to depression following chronic stress.

“The next step in this process is to come up with a drug that can target this receptor,” says Kirill Martemyanov, Ph.D., co-chair of the TSRI Department of Neuroscience and senior author of the new study, which is published in the journal eLife.

“We need to know what is happening in the brain so that we can develop more efficient therapies,” says Cesare Orlandi, Ph.D., the senior research associate at TSRI and co-first author of the study.

The researchers found elevated GPR158 protein in depressed patients, suspected it could play a major role in the disease process. They then conducted an animal study using male and female mice with and without above receptor. Subsequent behavioral tests showed that mice with elevated levels of GPR158 showed signs of depression following chronic stress and suppressing GPR158 protected them from developing depressive behavior and also resilient to stress.

Next, the researchers examined why GPR158 has these effects on depression. The team demonstrated that GPR158 affects key signaling pathways involved in mood regulation in the region of the brain called prefrontal cortex, though the researchers emphasized that the exact mechanisms remain to be established.

Martemyanov explains that GPR158 is a so-called “orphan receptor” (which gets its name because its binding partner/partners are unknown) with a poorly understood biology and mechanism of action. GPR158 appears to work downstream from other important brain systems, such as the GABA, a major player in the brain’s inhibitory control and adrenergic system involved in stress effects.

Laurie Sutton, Ph.D., a research associate at TSRI and co-first author of the study, says this finding matches what doctors have noticed in people who have experienced chronic stress. “There’s always a small population that is resilient they don’t show the depressive phenotype,” says Sutton.

As the search goes on for additional targets for depression, Martemyanov says scientists are increasingly using new tools in genome analysis to identify orphan receptors like GPR158. “Those are the untapped biology of our genomes, with significant potential for development of innovative therapeutics,” he says.

Citation: Sutton, Laurie P., Cesare Orlandi, Chenghui Song, Won Chan Oh, Brian S. Muntean, Keqiang Xie, Alice Filippini, Xiangyang Xie, Rachel Satterfield, Jazmine D W Yaeger, Kenneth J. Renner, Samuel M. Young, Baoji Xu, Hyungbae Kwon, and Kirill A. Martemyanov. “Orphan receptor GPR158 controls stress-induced depression.” ELife 7 (2018). doi:10.7554/elife.33273.

Research funding: National Institutes of Health, University of Iowa, Max Planck Society, Canadian Institutes of Health Research Fellowship.

Adapted from press release by the Scripps Research Institute.

Nutraceuticals, what are they? how we should regulate them?

A new review published in the British Journal of Clinical Pharmacology looks at the potential of nutraceuticals, stressing the need for a proper definition of nutraceuticals and clear regulations to ensure their safety.

In the review article, a team led by Ettore Novellino, PhD and Antonello Santini, PhD, of the University of Napoli Federico II in Italy, states that nutraceuticals with proven efficacy and health benefits substantiated by clinical data could be used as powerful tools to prevent and treat medical conditions, especially in individuals who may not yet be eligible for conventional pharmaceutical drugs.

The authors propose the following definition for nutraceuticals: the phytocomplex of a vegetable or the pool of secondary metabolites from an animal. Both are concentrated and administered in a pharmaceutical form and are capable of providing beneficial health effects, including the prevention and/or treatment of a disease.

“Nutraceuticals, in the collective imagination of the consumer, tend to be confused and wrongly identified with many other products available on the market on the basis of potential health benefits,” said Dr. Novellino. “An evaluation of the safety, the mechanism of action, and the effectiveness of nutraceuticals and substantiating this with clinical data is the central point that differentiates nutraceuticals from food supplements.”

Dr. Santini added that the growing demand and interest in nutraceuticals justifies the need for a restructuring of the entire regulatory framework that differentiates nutraceuticals from food supplements. “We propose a regulatory system that is similar to the one used for drugs, which is more rigorous and more complex than the one commonly accepted for food supplements,” he said. “It is important for consumer protection that national authorities and regulatory agencies require manufacturers to provide data to support any claim in the labels of products when the term nutraceutical is used.”

Citation: Santini, Antonello, Silvia Miriam Cammarata, Giacomo Capone, Angela Ianaro, Giancarlo Tenore, Luca Pani, and Ettore Novellino. “Nutraceuticals: opening the debate for a regulatory framework.” British Journal of Clinical Pharmacology, 2018. doi:10.1111/bcp.13496.

Adapted from press release by Wiley publications.