AMPA receptor subunit GluR2 gates injurious signals in ischemic stroke

  title={AMPA receptor subunit GluR2 gates injurious signals in ischemic stroke},
  author={Mangala Meenakshi Soundarapandian and Wei Tu and Peter Hsien Li Peng and Antonis Zervos and You Ming Lu},
  journal={Molecular Neurobiology},
Ischemic stroke, or a brain attack, is the third leading cause of death in developed countries. A critical feature of the disease is a highly selective pattern of neuronal loss; certain identifiable subsets of neurons—particularly CA1 pyramidal neurons in the hippocampus—are severely damaged, whereas others remain intact. A key step in this selective neuronal injury is Ca2+/Zn2+ entry into vulnerable neurons through α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptor channels… 
Distinct Subunit-specific α-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid (AMPA) Receptor Trafficking Mechanisms in Cultured Cortical and Hippocampal Neurons in Response to Oxygen and Glucose Deprivation*♦
Cultured cortical neurons are resistant to an OGD insult that causes cell death in hippocampal neurons, and the absence of OGD-induced GluA2 trafficking contributes to the relatively low vulnerability of cortical neurons to ischemia.
A Review of Glutamate Receptors II: Pathophysiology and Pathology
The diseases in which the pathophysiology and pathology are associated, in part, with the glutamate system are explored, including epilepsy, amnesia, anxiety, hyperalgesia and psychosis.
SPARC and GluA1-Containing AMPA Receptors Promote Neuronal Health Following CNS Injury
It is found that SPARC levels are increased in astrocytes and microglia following middle cerebral artery occlusion in vivo and oxygen-glucose deprivation in vitro and chronic pre-treatment with SPARC prevented OGD-induced loss of synaptic GluA1.
Direct interaction between GluR2 and GAPDH regulates AMPAR-mediated excitotoxicity
Disruption of GluR2/GAPDH interaction by administration of an interfering peptide prevents AMPAR-mediated excitotoxicity and protects against damage induced by oxygen-glucose deprivation, an in vitro model of brain ischemia.
P38 MAPK Inhibition Protects Against Glutamate Neurotoxicity and Modifies NMDA and AMPA Receptor Subunit Expression
Results showed that monosodium glutamate induces neuronal death and alters the expression of the subunits evaluated in the hippocampus at all ages studied, which suggests that selectively blocking the pro-death signaling pathway may reduce neuronal death in some neurodegenerative diseases in which these neurotoxic processes are present.
Subunit-specific trafficking mechanisms regulating the synaptic expression of Ca(2+)-permeable AMPA receptors.
  • J. G. Hanley
  • Biology
    Seminars in cell & developmental biology
  • 2014
PKA-Dependent Membrane Surface Recruitment of CI-AMPARs Is Crucial for BCP-Mediated Protection Against Post-acute Ischemic Stroke Cognitive Impairment
Data indicate that PKA-dependent synaptic membrane surface recruitment of CI-AMPARs is crucial for the neuroprotective effect of BCP against acute ischemic stroke and protection against post-acute isChemic stroke cognitive impairment.
TRPM7 Mediates Neuronal Cell Death Upstream of Calcium/Calmodulin-Dependent Protein Kinase II and Calcineurin Mechanism in Neonatal Hypoxic-Ischemic Brain Injury
A significant reduction of brain injury and improvement of short- and long-term functional outcomes after HI after administration of specific TRPM7 blocker waixenicin A are found.


GluR2-dependent properties of AMPA receptors determine the selective vulnerability of motor neurons to excitotoxicity.
Electrophysiological properties of AMPA receptors, known to be dependent on the relative abundance of GluR2: sensitivity to external polyamines, rectification index, and relative Ca(2+) permeability), correlated well with each other and with the selective vulnerability of motor neurons because motor neurons surviving an excitotoxic event had similar characteristics as dorsal horn neurons.
Molecular mechanisms of glutamate receptor-mediated excitotoxic neuronal cell death
The present review is aimed at summarizing the molecular mechanisms of NMDA receptor and AMPA/kainate receptor-mediated excitotoxic neuronal cell death.
Expression of Ca2+-Permeable AMPA Receptor Channels Primes Cell Death in Transient Forebrain Ischemia
Neuroprotection in Ischemia Blocking Calcium-Permeable Acid-Sensing Ion Channels
Global Ischemia Induces Downregulation of Glur2 mRNA and Increases AMPA Receptor-Mediated Ca2+ Influx in Hippocampal CA1 Neurons of Gerbil
Evidence is provided for Ca2+entry directly through AMPA receptors in pyramidal neurons destined to die in gerbil CA1 neurons after global ischemia, and downregulation of GluR2 gene expression and an increase inCa2+ influx through AM PA receptors in response to endogenous glutamate are likely to contribute to the delayed neuronal death after globalIschemia.
Knockdown of AMPA Receptor GluR2 Expression Causes Delayed Neurodegeneration and Increases Damage by Sublethal Ischemia in Hippocampal CA1 and CA3 Neurons
GluR2 antisense and brief sublethal global ischemia acted synergistically to cause degeneration of pyramidal neurons, consistent with action by a common mechanism.
Glutamate release in severe brain ischaemia is mainly by reversed uptake
It is demonstrated that transporter-mediated glutamate homeostasis fails dramatically in ischaemia: instead of removing extracellular glutamate to protect neurons, transporters release glutamate, triggering neuronal death.