Excitotoxicity and ALS: What is unique about the AMPA receptors expressed on spinal motor neurons?

  title={Excitotoxicity and ALS: What is unique about the AMPA receptors expressed on spinal motor neurons?},
  author={Yukio Kawahara and Shin Kwak},
  journal={Amyotrophic Lateral Sclerosis},
  pages={131 - 144}
It has been repeatedly reported that spinal motor neurons are selectively vulnerable to AMPA receptor‐mediated excitotoxicity. Therefore, identifying the uniqueness of AMPA receptors that are expressed on motor neurons, especially in individuals affected with sporadic amyotrophic lateral sclerosis (ALS) is essential for elucidating the etiology of this disorder. The mechanism that initiates motor neuronal death appears to be an exaggerated influx of Ca2+ through AMPA receptors. The determinants… 
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  • S. Rossi, V. De Chiara, D. Centonze
  • Biology
    Amyotrophic lateral sclerosis : official publication of the World Federation of Neurology Research Group on Motor Neuron Diseases
  • 2010
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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.
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The first quantitative measurements of the expression profile of AMPA receptor subunits mRNAs in human single neurons are provided by means of quantitative RT–PCR with a laser microdissector, showing that among the AMPA subunits, GluR2 shared the vast majority throughout the neuronal subsets and tissues examined.
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.
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