Abstract
In addition to its antioxidant properties arising from its ability to increase the formation of glutathione, N-acetylcysteine (NAC) is also a cystine prodrug that activates the cystine-glutamate exchanger (often referred to as system xc-). Via this latter mechanism, NAC modulates extracellular levels of glutamate, the predominant excitatory neurotransmitter in the central nervous system, making it a critical component of glutamate homeostasis in the central nervous system. As a result, NAC may have clinical efficacy in the treatment of various psychiatric and neurological disorders associated with dysregulated glutamate homeostasis. In this chapter, we first provide an overview of glutamatergic neurotransmission and regulation of extracellular glutamate by both excitatory amino acid transporters and system xc-. We then summarize the neurochemical mechanisms by which NAC regulates glutamate homeostasis. Finally, we discuss the mechanisms of action of newer NAC derivatives with respect to their interactions with glutamatergic transmission.
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Foster Olive, M., Powell, G., McClure, E., Gipson, C.D. (2019). Neurotransmitter Systems: Glutamate. In: Frye, R., Berk, M. (eds) The Therapeutic Use of N-Acetylcysteine (NAC) in Medicine. Adis, Singapore. https://doi.org/10.1007/978-981-10-5311-5_2
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DOI: https://doi.org/10.1007/978-981-10-5311-5_2
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