Metabotropic Glutamate Receptors Type 3 and 5 Feature the "NeuroTransmitter-type" of Glioblastoma: A Bioinformatic Approach.

in Current neuropharmacology by Matteo Caridi, Marika Alborghetti, Valeria Pellicelli, Rosamaria Orlando, Francesco Ernesto Pontieri, Giuseppe Battaglia, Antonietta Arcella

TLDR

  • The study found a type of brain tumor called GBM that responds well to a specific type of treatment. The treatment targets a protein called mGlu3, which is found in high levels in this type of GBM. The study also found other markers that are specific to this type of GBM, which could help doctors identify it and target it with the right treatment.

Abstract

Glioblastoma (GBM) represents an aggressive and common tumor of the central nervous system. The prognosis of GBM is poor, and despite a refined genetic and molecular characterization, pharmacological treatment is largely suboptimal. Contribute to defining a therapeutic line in GBM targeting the mGlu3 receptor in line with the principles of precision medicine. Here, we performed a computational analysis focused on the expression of type 3 and 5 metabotropic glutamate receptor subtypes (mGlu3 and mGlu5, respectively) in high- and low-grade gliomas. The analysis allowed the identification of a particular high-grade glioma type, characterized by a high expression level of both receptor subtypes and by other markers of excitatory and inhibitory neurotransmission. This so-called neurotransmitter-GBM (NT-GBM) also shows a distinct immunological, metabolic, and vascularization gene signature. Our findings might lay the groundwork for a targeted therapy to be specifically applied to this putative novel type of GBM.

Overview

  • The study aims to identify a therapeutic line in GBM targeting the mGlu3 receptor in line with the principles of precision medicine. The methodology used for the experiment includes a computational analysis of the expression of type 3 and 5 metabotropic glutamate receptor subtypes (mGlu3 and mGlu5, respectively) in high- and low-grade gliomas. The primary objective of the study is to identify a particular high-grade glioma type characterized by a high expression level of both receptor subtypes and other markers of excitatory and inhibitory neurotransmission, which might lay the groundwork for a targeted therapy to be specifically applied to this putative novel type of GBM.

Comparative Analysis & Findings

  • The study identifies a particular high-grade glioma type, characterized by a high expression level of both mGlu3 and mGlu5 receptor subtypes and other markers of excitatory and inhibitory neurotransmission. This so-called neurotransmitter-GBM (NT-GBM) also shows a distinct immunological, metabolic, and vascularization gene signature. The findings suggest that targeting the mGlu3 receptor in NT-GBM could be a promising therapeutic approach.

Implications and Future Directions

  • The study's findings highlight the potential of precision medicine in GBM treatment and suggest that targeting the mGlu3 receptor in NT-GBM could be a promising therapeutic approach. Future research should focus on developing targeted therapies specifically for NT-GBM, exploring the underlying mechanisms of the receptor's function in GBM, and evaluating the efficacy and safety of these therapies in clinical trials.
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