title: Novel etiological and therapeutic strategies for neurodiseases: RNA editing enzyme abnormality in sporadic amyotrophic lateral sclerosis.
abstract: 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.
authors.affiliation: Department of Neurology, Graduate School of Medicine, The University of Tokyo, Japan. hideyamat-int@h.u-tokyo.ac.jp
authors.forename: Takuto
authors.initials: T
authors.lastname: Hideyama
authors.forename: Takenari
authors.initials: T
authors.lastname: Yamashita
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Nishimoto
authors.forename: Takeshi
authors.initials: T
authors.lastname: Suzuki
authors.forename: Shin
authors.initials: S
authors.lastname: Kwak
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics*; D000243:Adenosine Deaminase / Q000235:genetics* / Q000378:metabolism; D000690:Amyotrophic Lateral Sclerosis / Q000201:enzymology / Q000235:genetics*; D000818:Animals; D016923:Cell Death / Q000235:genetics; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D008954:Models, Biological; D009046:Motor Neurons / Q000378:metabolism*; D017393:RNA Editing; D016601:RNA-Binding Proteins; D018091:Receptors, AMPA / Q000235:genetics
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C518673:CYFIP2 protein, human; D016601:RNA-Binding Proteins; D018091:Receptors, AMPA; C567955:ADARB1 protein, human; D000243:Adenosine Deaminase; C104722:glutamate receptor ionotropic, AMPA 2