Ionotropic receptors in the central nervous system and neurodegenerative disease

Nady Braidy, Anne Poljak, Tharusha Jayasena, Gilles J. Guillemin, Perminder Sachdev

Research output: Chapter in Book/Report/Conference proceedingChapter

1 Citation (Scopus)

Abstract

Glutamate was identified as the main excitatory neurotransmitter in the mammalian central nervous system (CNS) following the observation in the early 1950s that glutamate can induce seizure activity and excite neurons in the mammalian brain. Over the last two decades, selective ligands, including competitive agonists and antagonists and allosteric modulators, have been developed to further investigate the functional role of glutaminergic receptors. Glutamate released from synapses can activate ligand-gated cation channels at postsynaptic cells to mediate fast postsynaptic potentials. These ion channel-forming ionotropic glutamate receptors (iGluRs) are divided into N-methyl-D-aspartate (NMDA), α-amino-3-hydroxyl-5-methyl-isoxazole-4-prorionate (AMPA), and kainate (KA) receptors. While only 20–30 % of the amino acid sequence is shared among these receptor subtypes, they share similar structural features and their activity is based on specific pharmacological preference. In this chapter, we will describe the structure and composition of iGluRs and infer their pharmacology, with a particular focus on their role in the CNS and their relevance to the pathogenesis of neurodegenerative diseases.
Original languageEnglish
Title of host publicationHandbook of neurotoxicity
EditorsRichard M Kostrzewa
Place of PublicationNew York
PublisherSpringer, Springer Nature
Pages1071-1092
Number of pages22
ISBN (Electronic)9781461458364
ISBN (Print)9781461458357
DOIs
Publication statusPublished - 2014

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    Braidy, N., Poljak, A., Jayasena, T., Guillemin, G. J., & Sachdev, P. (2014). Ionotropic receptors in the central nervous system and neurodegenerative disease. In R. M. Kostrzewa (Ed.), Handbook of neurotoxicity (pp. 1071-1092). New York: Springer, Springer Nature. https://doi.org/10.1007/978-1-4614-5836-4_126