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	Takuto Hideyama, Takenari Yamashita, Yoshinori Nishimoto, Takeshi Suzuki, Shin Kwak
Journal	Journal of pharmacological sciences (J Pharmacol Sci) Vol. 113 Issue 1 Pg. 9-13 ( 2010) ISSN: 1347-8648 [Electronic] Japan
PMID	20424386 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Review)
Chemical References	Adaptor Proteins, Signal Transducing CYFIP2 protein, human RNA-Binding Proteins Receptors, AMPA ADARB1 protein, human Adenosine Deaminase glutamate receptor ionotropic, AMPA 2
Topics	Adaptor Proteins, Signal Transducing (genetics) Adenosine Deaminase (genetics, metabolism) Amyotrophic Lateral Sclerosis (enzymology, genetics) Animals Cell Death (genetics) Humans Mice Mice, Knockout Models, Biological Motor Neurons (metabolism) RNA Editing RNA-Binding Proteins Receptors, AMPA (genetics)

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