Deficient RNA editing of GluR2 and neuronal death in amyotropic lateral sclerosis

  title={Deficient RNA editing of GluR2 and neuronal death in amyotropic lateral sclerosis},
  author={Shin Kwak and Yukio Kawahara},
  journal={Journal of Molecular Medicine},
One plausible hypothesis for selective neuronal death in sporadic amyotropic lateral sclerosis (ALS) is excitotoxicity mediated by α-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) receptors, which are a subtype of ionotropic glutamate receptors. The Ca2+ conductance of AMPA receptors differs markedly depending on whether the GluR2 (or GluR-B) subunit is a component of the receptor. The properties of GluR2 are generated posttranscriptionally by RNA editing at the Q/R site in the putative… 

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.

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

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.

Induced Loss of ADAR2 Engenders Slow Death of Motor Neurons from Q/R Site-Unedited GluR2

GluR2 Q/R site editing causes AMPA receptor-mediated death of motor neurons in genetically modified mice and shows a decline in motor function commensurate with the slow death of ADAR2-deficient motor neurons.

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.

Hippocampus-specific deficiency in RNA editing of GluA2 in Alzheimer's disease

Glutamate receptor RNA editing in health and disease

Overall, these data indicate that a highly regulated process of glutamate receptor editing is of key importance in the proper function of neuronal cells and in their ability to adapt and modulate synaptic function.

Testing of the therapeutic efficacy and safety of AMPA receptor RNA aptamers in an ALS mouse model

A 12-wk continuous, intracerebroventricular infusion of aptamers to AR2 mice reduced the progression of motor dysfunction, normalized TDP-43 mislocalization, and prevented death of motor neurons.



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.

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.

Q/R editing of the rat GluR5 and GluR6 kainate receptors in vivo and in vitro: evidence for independent developmental, pathological and cellular regulation

It is shown that in’vivo, Q/R editing in the GluR5 and GLUR6 mRNAs is modulated during ontogeny and differs substantially in a variety of nervous tissues, and suggests that editing of these mRNas is not co‐regulated.

Dramatic Increase of the RNA Editing for Glutamate Receptor Subunits During Terminal Differentiation of Clonal Human Neurons

The change of the RNA editing of GluR subunits in conjunction with the expression of two DRADA members, DRADA1 and DRADA2 genes, during neuronal differentiation is investigated using a human teratocarcinoma cell line, NT2.

Underediting of glutamate receptor GluR-B mRNA in malignant gliomas

It is reported that in tissues from malignant human brain tumors, this editing position of glutamate receptor subunit B is substantially underedited compared with control tissues, suggesting a role for RNA editing in tumor progression and providing a molecular model explaining the occurrence of epileptic seizures in association with malignant gliomas.

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

Assessing the Extent of RNA Editing in the TMII Regions of GluR5 and GluR6 Kainate Receptors During Rat Brain Development

It is shown that editing in both GluRS and GluR6 RNA is developmentally regulated and that different regions of the adult rat hippocampus demonstrate distinct levels of GLUR6 editing.

Editing of GluR2 RNA in the Gerbil Hippocampus after Global Cerebral Ischemia

Results clearly demonstrate that global ischemia does not cause impairment of GluR2 RNA editing, which is thus not responsible for the abnormal calcium permeability of the postischemic cell membrane.