Novel etiological and therapeutic strategies for neurodiseases: RNA editing enzyme abnormality in sporadic amyotrophic lateral sclerosis

Takuto Hideyama, Takenari Yamashita, Yoshinori Nishimoto, Takeshi Suzuki, Shin Kwak

Research output: Contribution to journalReview article

6 Citations (Scopus)


The motor neurons of patients with sporadic amyotrophic lateral sclerosis (ALS) express abundant Q/R site-unedited GluR2 mRNA, whereas those of patients with other motor neuron diseases including familial ALS associated with mutated SOD1 (ALS1) and those of normal subjects express only Q/R site-edited GluR2 mRNA. Because adenosine deaminase acting on RNA type 2 (ADAR2) specifically catalyzes GluR2 Q/R site-editing, it is likely that ADAR2 activity is not sufficient to edit this site completely in motor neurons of patients with sporadic ALS. Because these molecular abnormalities occur in disease-and motor neuron-specific fashion and induce fatal epilepsy in mice, we have hypothesized that GluR2 Q/R site-underediting due to ADAR2 underactivity is a cause of neuronal death in sporadic ALS. We found that cytoplasmic fragile X mental retardation protein interacting protein 2 (CYFIP2) mRNA had an ADAR2-mediated editing position using RNA interference knockdown. Our review will include a discussion of new ADAR2 substrates that may be useful for research on sporadic ALS.

Original languageEnglish
Pages (from-to)9-13
Number of pages5
JournalJournal of Pharmacological Sciences
Issue number1
Publication statusPublished - 2010 May 17



  • Amyotrophic lateral sclerosis (ALS)
  • Cytoplasmic fragile X mental retardation protein interacting protein 2 (CYFIP2)
  • GluR2 Q/R
  • Neurodisease
  • RNA editing
  • α-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) receptor

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology

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