This review focused exclusively on NAAG research in the mammalian nervous system. For NAAG-related research in crayfish, see the very interesting work of A. K. Urazaev, R. M. Grossfeld, and E. M. Lieberman.
Advances in understanding the peptide neurotransmitter NAAG and appearance of a new member of the NAAG neuropeptide family
Article first published online: 1 JUL 2011
© 2011 The Authors. Journal of Neurochemistry © 2011 International Society for Neurochemistry
Journal of Neurochemistry
Volume 118, Issue 4, pages 490–498, August 2011
How to Cite
Neale, J. H., Olszewski, R. T., Zuo, D., Janczura, K. J., Profaci, C. P., Lavin, K. M., Madore, J. C. and Bzdega, T. (2011), Advances in understanding the peptide neurotransmitter NAAG and appearance of a new member of the NAAG neuropeptide family. Journal of Neurochemistry, 118: 490–498. doi: 10.1111/j.1471-4159.2011.07338.x
- Issue published online: 14 JUL 2011
- Article first published online: 1 JUL 2011
- Accepted manuscript online: 6 JUN 2011 09:22AM EST
- Received May 3, 2011; revised manuscript received May 26, 2011; accepted May 27, 2011.
- inflammatory pain;
- metabotropic glutamate receptor 3;
J. Neurochem. (2011) 118, 490–498.
A substantial body of data was reported between 1984 and 2000 demonstrating that the neuropeptide N-acetylaspartylglutamate (NAAG) not only functions as a neurotransmitter but also is the third most prevalent transmitter in the mammalian nervous system behind glutamate and GABA. By 2005, this conclusion was validated further through a series of studies in vivo and in vitro. The primary enzyme responsible for the inactivation of NAAG following its synaptic release had been cloned, characterized and knocked out. Potent inhibitors of this enzyme were developed and their efficacy has been extensively studied in a series of animal models of clinical conditions, including stroke, peripheral neuropathy, traumatic brain injury, inflammatory and neuropathic pain, cocaine addiction, and schizophrenia. Considerable progress also has been made in defining further the mechanism of action of these peptidase inhibitors in elevating synaptic levels of NAAG with the consequent inhibition of transmitter release via the activation of pre-synaptic metabotropic glutamate receptor 3 by this peptide. Very recent discoveries include identification of two different nervous system enzymes that mediate the synthesis of NAAG from N-acetylaspartate and glutamate and the finding that one of these enzymes also mediates the synthesis of a second member of the NAAG family of neuropeptides, N-acetylaspartylglutamylglutamate.