Human spinal motoneurons express low relative abundance of GluR2 mRNA: an implication for excitotoxicity in ALS

  title={Human spinal motoneurons express low relative abundance of GluR2 mRNA: an implication for excitotoxicity in ALS},
  author={Yukio Kawahara and Shin Kwak and Hui Sun and Kyoko Ito and Hideji Hashida and Hitoshi Aizawa and Seon‐Yong Jeong and Ichiro Kanazawa},
  journal={Journal of Neurochemistry},
AMPA receptor‐mediated neurotoxicity is currently the most plausible hypothesis for the etiology of amyotrophic lateral sclerosis (ALS). The mechanism initiating this type of neuronal death is believed to be exaggerated Ca2+‐influx through AMPA receptors, which is critically determined by the presence or absence of the glutamate receptor subunit 2 (GluR2) in the assembly. We have provided the first quantitative measurements of the expression profile of AMPA receptor subunits mRNAs in human… 
Excitotoxicity and ALS: What is unique about the AMPA receptors expressed on spinal motor neurons?
  • Y. Kawahara, S. Kwak
  • Biology
    Amyotrophic lateral sclerosis and other motor neuron disorders : official publication of the World Federation of Neurology, Research Group on Motor Neuron Diseases
  • 2005
This review focuses on recent progress on the molecular dynamics of AMPA receptors and discusses the pathophysiology of selective motor neuron death mediated by AM PA receptors in individuals affected with sporadic ALS.
Altered presymptomatic AMPA and cannabinoid receptor trafficking in motor neurons of ALS model mice: implications for excitotoxicity
To the knowledge, this is the first demonstration of presymptomatic changes in trafficking of receptors that are in direct control of excitotoxicity and death in a mouse model of ALS.
Deficient RNA editing of GluR2 and neuronal death in amyotropic lateral sclerosis
GluR2 underediting occurs in a disease specific and region selective manner and is likely that the molecular mechanism underlying the deficiency in RNA editing is a reduction in the activity of ADAR2, a double- strand RNA specific deaminase.
GluR2 Deficiency Accelerates Motor Neuron Degeneration in a Mouse Model of Amyotrophic Lateral Sclerosis
It is indicated that GluR2 plays a pivotal role in the vulnerability of motor neurons in vitro and in vivo, and that therapies that limit Ca2+ entry through AMPA receptors might be beneficial in ALS patients.
The cellular mRNA expression of GABA and glutamate receptors in spinal motor neurons of SOD1 mice
Evidence for low GluR2 AMPA receptor subunit expression at synapses in the rat basolateral amygdala
Although BLA principal neurons express perikaryal and proximal dendritic GluR2 immunoreactivity, few synapses onto these neurons express Glu R2, and a preponderance of principal neurons have inwardly rectifying AMPA‐mediated synaptic currents, suggesting that targeting of Glur2 to synapses is restricted.
Role of excitotoxicity in the degeneration of motor neurones in ALS.
Results suggest that AMPA receptor mediated excitotoxicity is a primary cause of motor neurone degeneration in ALS and may contribute to the development of new therapeutic strategies for this devastating disease.


GluR2 AMPA Receptor Subunit Expression in Motoneurons at Low and High Risk for Degeneration in Amyotrophic Lateral Sclerosis
Exchange of GluR2 mRNA and protein in motoneurons that differ in their vulnerability to degeneration in ALS suggests that reduced expression of GLUR2 is not a factor predisposing mot oneurons to degenerations.
AMPA Receptor Calcium Permeability, GluR2 Expression, and Selective Motoneuron Vulnerability
The results indicate that the selective vulnerability of motoneurons to AMPA receptor agonists is not determined solely by whole-cell relative Ca2+ permeability of AMPA receptors.
Characterization of the AMPA‐Activated Receptors Present on Motoneurons
The data show that despite high levels of edited GluR2 mRNA, some AMPARs are Ca2+‐permeable, and this subset of AM PARs can account for the AMPAR‐mediated Ca2- inflow inferred from cobalt uptake and electrophysiology studies.
Low expression of GluR2 AMPA receptor subunit protein by human motor neurons.
It is likely that human motor neurons express a high proportion of atypical, calcium permeable AMPA receptors which may contribute to selective vulnerability and may allow cell-specific modulation of the actions of glutamate.
The Influence of Glutamate Receptor 2 Expression on Excitotoxicity in GluR2 Null Mutant Mice
AMPA receptor (AMPAR)-mediated ionic currents that govern gene expression, synaptic strength, and plasticity also can trigger excitotoxicity. However, native AMPARs exhibit heterogeneous
Reduction of GluR2 RNA editing, a molecular change that increases calcium influx through AMPA receptors, selective in the spinal ventral gray of patients with amyotrophic lateral sclerosis
The decrement of GluR2 mRNA editing efficiency is unique to the ventral gray of ALS cases and may be closely linked to the etiology of ALS.
Motor Neurons Are Selectively Vulnerable to AMPA/Kainate Receptor-Mediated Injury In Vitro
Large SMI-32(+) neurons are selectively damaged by prolonged (24 hr) low-level exposures to kainate or to the glutamate reuptake blockerl-trans-pyrrolidine-2,4-dicarboxylic acid, suggesting that Ca2+ ions are also important in this more slowly evolving injury.
Alterations in AMPA Receptor Subunit Expression after Experimental Spinal Cord Contusion Injury
The AMPA-preferring subtype of ionotropic glutamate receptors (GluRs) is a hetero-oligomeric ion channel assembled from various combinations of four subunits: GluR1, GluR2, GluR3, and GluR4.