A role for N-acetylaspartylglutamate (NAAG) and mGluR3 in cognition

Neurobiol Learn Mem. 2019 Feb:158:9-13. doi: 10.1016/j.nlm.2019.01.006. Epub 2019 Jan 7.

Abstract

The peptide transmitter N-acetylaspartylglutamate (NAAG) and its receptor, the type 3 metabotropic glutamate receptor (mGluR3, GRM3), are prevalent and widely distributed in the mammalian nervous system. Drugs that inhibit the inactivation of synaptically released NAAG have procognitive activity in object recognition and other behavioral models. These inhibitors also reverse cognitive deficits in animal models of clinical disorders. Antagonists of mGluR3 block these actions and mice that are null mutant for this receptor are insensitive to the actions of these procognitive drugs. A positive allosteric modulator of this receptor also has procognitive activity. While some data suggest that drugs acting on mGluR3 achieve their procognitive action by increasing arousal during acquisition training, exploration of the procognitive efficacy of NAAG is in its early stages and thus substantial opportunities exist to define the breadth and nature of this activity.

Keywords: Glutamate carboxypeptidase II; Memory; Metabotropic receptors; N-acetylaspartylglutamate; NAAG; mGluR3.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Cognition / drug effects
  • Cognition / physiology*
  • Dipeptides / physiology*
  • Glutamate Carboxypeptidase II / drug effects
  • Glutamate Carboxypeptidase II / physiology*
  • Memory / drug effects
  • Memory / physiology*
  • Receptors, Metabotropic Glutamate / antagonists & inhibitors
  • Receptors, Metabotropic Glutamate / physiology*

Substances

  • Dipeptides
  • Receptors, Metabotropic Glutamate
  • metabotropic glutamate receptor 3
  • isospaglumic acid
  • Glutamate Carboxypeptidase II