Excitotoxicity and stroke: identifying novel targets for neuroprotection

Progress in Neurobiology
Ted Weita LaiYu Tian Wang

Abstract

Excitotoxicity, the specific type of neurotoxicity mediated by glutamate, may be the missing link between ischemia and neuronal death, and intervening the mechanistic steps that lead to excitotoxicity can prevent stroke damage. Interest in excitotoxicity began fifty years ago when monosodium glutamate was found to be neurotoxic. Evidence soon demonstrated that glutamate is not only the primary excitatory neurotransmitter in the adult brain, but also a critical transmitter for signaling neurons to degenerate following stroke. The finding led to a number of clinical trials that tested inhibitors of excitotoxicity in stroke patients. Glutamate exerts its function in large by activating the calcium-permeable ionotropic NMDA receptor (NMDAR), and different subpopulations of the NMDAR may generate different functional outputs, depending on the signaling proteins directly bound or indirectly coupled to its large cytoplasmic tail. Synaptic activity activates the GluN2A subunit-containing NMDAR, leading to activation of the pro-survival signaling proteins Akt, ERK, and CREB. During a brief episode of ischemia, the extracellular glutamate concentration rises abruptly, and stimulation of the GluN2B-containing NMDAR in the extrasynaptic si...Continue Reading

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Citations

Jan 8, 2016·Trends in Endocrinology and Metabolism : TEM·Silke Otter, Eckhard Lammert
Jul 22, 2015·International Journal of Molecular Sciences·Liang ZhuAiguo Shen
Jan 8, 2016·International Journal of Molecular Sciences·Raymond Shim, Connie H Y Wong
Feb 16, 2016·Brain Research Bulletin·Changwei ZhouQingpeng Liu
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