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Editorial
. 2011 Dec;119(5):891-5.
doi: 10.1111/j.1471-4159.2011.07380.x.

N-acetylaspartylglutamate is an agonist at mGluR₃ in vivo and in vitro

Joseph H Neale
Editorial

N-acetylaspartylglutamate is an agonist at mGluR₃ in vivo and in vitro

Joseph H Neale. J Neurochem. 2011 Dec.
No abstract available

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Figures

Figure 1
Figure 1. A model of the role of NAAG peptidase inhibition and its influence on NAAG and NAAG2 in the nervous system (From Neale et al., 2011)
A. Neurons expressing NAAG synthetase I (NAAGS I) mediate the synthesis of NAAG but not NAAG2. In this cell, NAAG is co-released with a primary amine transmitter, such as glutamate, under conditions of elevated neuronal activity. NAAG is released into the perisynaptic space where it activates presynaptic and glial type 3 metabotropic glutamate receptors (mGluR3). NAAG is inactivated by glutamate carboxypeptidases II (GCPII) and III (GCPIII), forming N-acetylaspartate (NAA) and glutamate (Glu), which are transported into glial cells. Inhibition of the peptidases GCPII and GCPIII by a NAAG peptidase inhibitor, such as ZJ43, reduces inactivation of NAAG and raises perisynaptic NAAG level. In animal models, the NAAG peptidase inhibitor-mediated elevation of peptide levels increases the activation of mGluR3 receptors on axon endings, inhibiting transmitter release and reducing pathology. In a second neuroprotective pathway, NAAG activation of mGlu3 receptors on glial cells stimulates the release of a trophic factor, transforming growth factor β (TGF-β). B. Neuron synthesizing NAAG2 via NAAG synthetase II (NAAGS II) may release both NAAG and NAAG2.
Figure 1
Figure 1. A model of the role of NAAG peptidase inhibition and its influence on NAAG and NAAG2 in the nervous system (From Neale et al., 2011)
A. Neurons expressing NAAG synthetase I (NAAGS I) mediate the synthesis of NAAG but not NAAG2. In this cell, NAAG is co-released with a primary amine transmitter, such as glutamate, under conditions of elevated neuronal activity. NAAG is released into the perisynaptic space where it activates presynaptic and glial type 3 metabotropic glutamate receptors (mGluR3). NAAG is inactivated by glutamate carboxypeptidases II (GCPII) and III (GCPIII), forming N-acetylaspartate (NAA) and glutamate (Glu), which are transported into glial cells. Inhibition of the peptidases GCPII and GCPIII by a NAAG peptidase inhibitor, such as ZJ43, reduces inactivation of NAAG and raises perisynaptic NAAG level. In animal models, the NAAG peptidase inhibitor-mediated elevation of peptide levels increases the activation of mGluR3 receptors on axon endings, inhibiting transmitter release and reducing pathology. In a second neuroprotective pathway, NAAG activation of mGlu3 receptors on glial cells stimulates the release of a trophic factor, transforming growth factor β (TGF-β). B. Neuron synthesizing NAAG2 via NAAG synthetase II (NAAGS II) may release both NAAG and NAAG2.
See this image and copyright information in PMC

References

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