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

  title={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},
  author={Hiroshi Takuma and Shin Kwak and Toshihiro Yoshizawa and Ichiro Kanazawa},
  journal={Annals of Neurology},
Enhancement of calcium influx through the α‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazolepropionate (AMPA)/kainate receptor is a plausible mechanism underlying selective neuronal death in amyotrophic lateral sclerosis (ALS). The calcium conductance of the AMPA receptor is regulated by the GluR2 subunit that is edited at the glutamine/arginine residue site in the subunit assembly. We investigated the molecular changes of GluR2 mRNA in the spinal cord of ALS cases, those of cases with other neurological… 

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.

Profound downregulation of the RNA editing enzyme ADAR2 in ALS spinal motor neurons

The essential role of AMPA receptor GluR2 subunit RNA editing in the normal and diseased brain

It is suggested that further studies of the role of unedited GLUA2 in normal brain function and disease are warranted, and that GluA2 editing should be considered as a possible contributing factor when Ca2+-permeable AMPA receptors are observed.

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

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.

Investigating RNA editing in the pathogenesis of Amyotrophic Lateral Sclerosis

It was demonstrated that GLUR2 was fully edited in the MNs of ALS/C9ORF72- positive, ALS/ c9ORf72-negative cases and controls, and full editing of GLur2 in dissected motor neurons isolated by LCM was confirmed.

Altered Intracellular Milieu of ADAR2-Deficient Motor Neurons in Amyotrophic Lateral Sclerosis

The evidence indicates that ADAR2 downregulation is a causative factor in ALS, and AR2 mice exhibit causative molecular changes that occur inALS, and normalization of disrupted intracellular environments resulting from ADAR1 downregulation may be a therapeutic target for ALS.

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

  • Y. KawaharaS. 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.

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.



Differential RNA editing efficiency of AMPA receptor subunit GluR-2 in human brain.

This work provides the first evidence that this RNA editing phenomenon occurs in human brain and is differentially regulated, and has important implications in AMPA receptor channel-mediated calcium influx.

Ischaemia does not alter the editing status at the Q/R site of glutamate receptor‐A, ‐B, ‐5 and ‐6 subunit mRNA

It is concluded that delayed neuronal cell death is not mediated by a less selective or less efficient mRNA editing process of the different glutamate receptor subunits in the hippocampus.

Calcium‐permeable α‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazole propionic acid receptors: A molecular determinant of selective vulnerability in amyotrophic lateral sclerosis

The cause of the selective degeneration of motor neurons in amyotrophic lateral sclerosis (ALS) remains unexplained. One potential pathogenetic mechanism is chronic toxicity due to disturbances of

RNA Editing of the Glutamate Receptor Subunits GluR2 and GluR6 in Human Brain Tissue

It is indicated that RNA editing is seen in human brain as well as rat brain and that the extent of editing is similar in Huntington's disease compared with controls.

Neurological dysfunctions in mice expressing different levels of the Q/R site–unedited AMPAR subunit GluR–B

Mouse mutants with targeted AMPA receptor GluR–B subunit alleles, functionally expressed at different levels and deficient in Q/R–site editing have mild to severe neurological dysfunctions, including epilepsy and deficits in dendritic architecture.