Novel Etiological and Therapeutic Strategies for Neurodiseases: RNA Editing Enzyme Abnormality in Sporadic Amyotrophic Lateral Sclerosis
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概要
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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.
著者
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SUZUKI Takeshi
Division of Epidemiology and Prevention, Aichi Cancer Center Research Institute
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KWAK Shin
Department of Neurology, University of Tokyo Hospital
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Kwak Shin
Department Of Neurology Graduate School Of Medicine The University Of Tokyo
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HIDEYAMA Takuto
Department of Neurology, Graduate School of Medicine, The University of Tokyo
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Hideyama Takuto
Department Of Neurology Graduate School Of Medicine The University Of Tokyo
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Yamashita Takenari
Department of Neurology, Graduate School of Medicine, The University of Tokyo, Japan
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Nishimoto Yoshinori
Deptartment of Neurology, School of Medicine, Keio University, Japan
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Yamashita Takenari
Department Of Neurology Graduate School Of Medicine The University Of Tokyo
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Nishimoto Yoshinori
Department Of Neurology School Of Medicine Keio University
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Suzuki Takeshi
Division Of Basic Biological Sciences Faculty Of Pharmacy Keio University
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Kwak Shin
Department of Neurology, Graduate School of Medicine, The University of Tokyo, Japan
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