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

Curr Neuropharmacol. 2024;22(11):1923-1939. doi: 10.2174/1570159X22666240320112926.

Abstract

Background: 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.

Objective: Contribute to defining a therapeutic line in GBM targeting the mGlu3 receptor in line with the principles of precision medicine.

Methods: 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.

Results: 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.

Conclusion: Our findings might lay the groundwork for a targeted therapy to be specifically applied to this putative novel type of GBM.

Keywords: Glioma; glioblastoma multiforme; glutamate; immunological signature; metabolic signature.; metabotropic glutamate receptors type 3 and type 5; neurotransmitter- GBM.

MeSH terms

  • Brain Neoplasms* / genetics
  • Brain Neoplasms* / metabolism
  • Computational Biology*
  • Glioblastoma* / genetics
  • Glioblastoma* / metabolism
  • Humans
  • Neurotransmitter Agents / metabolism
  • Receptor, Metabotropic Glutamate 5 / metabolism
  • Receptors, Metabotropic Glutamate* / genetics
  • Receptors, Metabotropic Glutamate* / metabolism

Substances

  • Receptors, Metabotropic Glutamate
  • metabotropic glutamate receptor 3
  • Receptor, Metabotropic Glutamate 5
  • Neurotransmitter Agents