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d-Aspartate acts as a signaling molecule in nervous and neuroendocrine systems

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Abstract

d-Aspartate (d-Asp) is an endogenous amino acid in the central nervous and reproductive systems of vertebrates and invertebrates. High concentrations of d-Asp are found in distinct anatomical locations, suggesting that it has specific physiological roles in animals. Many of the characteristics of d-Asp have been documented, including its tissue and cellular distribution, formation and degradation, as well as the responses elicited by d-Asp application. d-Asp performs important roles related to nervous system development and hormone regulation; in addition, it appears to act as a cell-to-cell signaling molecule. Recent studies have shown that d-Asp fulfills many, if not all, of the definitions of a classical neurotransmitter—that the molecule’s biosynthesis, degradation, uptake, and release take place within the presynaptic neuron, and that it triggers a response in the postsynaptic neuron after its release. Accumulating evidence suggests that these criteria are met by a heterogeneous distribution of enzymes for d-Asp’s biosynthesis and degradation, an appropriate uptake mechanism, localization within synaptic vesicles, and a postsynaptic response via an ionotropic receptor. Although d-Asp receptors remain to be characterized, the postsynaptic response of d-Asp has been studied and several l-glutamate receptors are known to respond to d-Asp. In this review, we discuss the current status of research on d-Asp in neuronal and neuroendocrine systems, and highlight results that support d-Asp’s role as a signaling molecule.

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Acknowledgments

This work was supported by Award Number R01 NS031609 from National Institute of Neurological Disorders and Stroke, Award Number P30 DA018310 from the National Institute on Drug Abuse, and Award Number CHE-11-11705 from the National Science Foundation. The content is solely the responsibility of the authors and does not necessarily represent the official views of the award agencies.

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  1. Ting Shi

    Present address: Bristol-Myers Squibb, Princeton, NJ, USA

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  1. Department of Chemistry and Beckman Institute, University of Illinois at Urbana-Champaign, Urbana, USA

    Nobutoshi Ota, Ting Shi & Jonathan V. Sweedler

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  1. Nobutoshi Ota
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Ota, N., Shi, T. & Sweedler, J.V. d-Aspartate acts as a signaling molecule in nervous and neuroendocrine systems. Amino Acids 43, 1873–1886 (2012). https://doi.org/10.1007/s00726-012-1364-1

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