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 etal., (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.
Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
