title: AMPA-receptor trafficking and injury-induced cell death.
abstract: AMPA receptors (AMPARs) are critical for synaptic plasticity, and are subject to alterations based on subunit composition and receptor trafficking to and from the plasma membrane. One of the most potent regulators of AMPAR trafficking is the pro-inflammatory cytokine tumor necrosis factor (TNF)α, which is involved in physiological regulation of synaptic strength (Beattie et al., (2002) Science, 295, 2282-2285; Stellwagen and Malenka, (2006) Nature, 440, 1054-1059) and is also present at high concentrations after CNS injury. Here, we review evidence that TNF can rapidly alter the surface expression of AMPARs so that the proportion of Ca(++) -permeable receptors is increased and that this increase, in combination with increased levels of extracellular glutamate after injury, plays an important role in enhancing excitotoxic cell death after CNS injury. Thus, the pathophysiological hijacking of a critical regulator of synaptic plasticity and homeostasis by the secondary injury cascade may represent a new therapeutic target for neuroprotection.
authors.affiliation: Brain and Spinal Injury Center, Department of Neurological Surgery, University of California, San Francisco, Bldg. 1, Rm 101, San Francisco, CA 94110, USA. michael.beattie@ucsf.edu
authors.forename: Michael S
authors.initials: MS
authors.lastname: Beattie
authors.forename: Adam R
authors.initials: AR
authors.lastname: Ferguson
authors.forename: Jacqueline C
authors.initials: JC
authors.lastname: Bresnahan
mesh_terms: D000818:Animals; D016923:Cell Death / Q000502:physiology; D002490:Central Nervous System / Q000293:injuries* / Q000378:metabolism; D018698:Glutamic Acid / Q000378:metabolism; D006801:Humans; D009473:Neuronal Plasticity / Q000502:physiology*; D021381:Protein Transport / Q000502:physiology; D018091:Receptors, AMPA / Q000378:metabolism*; D013569:Synapses / Q000502:physiology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D018091:Receptors, AMPA; D014409:Tumor Necrosis Factor-alpha; D018698:Glutamic Acid