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01-07-2010 | Original Paper

TDP-43 pathology in sporadic ALS occurs in motor neurons lacking the RNA editing enzyme ADAR2

Authors: Hitoshi Aizawa, Jun Sawada, Takuto Hideyama, Takenari Yamashita, Takayuki Katayama, Naoyuki Hasebe, Takashi Kimura, Osamu Yahara, Shin Kwak

Published in: Acta Neuropathologica | Issue 1/2010

Abstract

Both the appearance of cytoplasmic inclusions containing phosphorylated TAR DNA-binding protein (TDP-43) and inefficient RNA editing at the GluR2 Q/R site are molecular abnormalities observed specifically in motor neurons of patients with sporadic amyotrophic lateral sclerosis (ALS). The purpose of this study is to determine whether a link exists between these two specific molecular changes in ALS spinal motor neurons. We immunohistochemically examined the expression of adenosine deaminase acting on RNA 2 (ADAR2), the enzyme that specifically catalyzes GluR2 Q/R site-editing, and the expression of phosphorylated and non-phosphorylated TDP-43 in the spinal motor neurons of patients with sporadic ALS. We found that all motor neurons were ADAR2-positive in the control cases, whereas more than half of them were ADAR2-negative in the ALS cases. All ADAR2-negative neurons had cytoplasmic inclusions that were immunoreactive to phosphorylated TDP-43, but lacked non-phosphorylated TDP-43 in the nucleus. Our results suggest a molecular link between reduced ADAR2 activity and TDP-43 pathology.

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Title: TDP-43 pathology in sporadic ALS occurs in motor neurons lacking the RNA editing enzyme ADAR2
Authors: Hitoshi Aizawa
Jun Sawada
Takuto Hideyama
Takenari Yamashita
Takayuki Katayama
Naoyuki Hasebe
Takashi Kimura
Osamu Yahara
Shin Kwak
Publication date: 01-07-2010
Publisher: Springer-Verlag
Published in: Acta Neuropathologica / Issue 1/2010
Print ISSN: 0001-6322
Electronic ISSN: 1432-0533
DOI: https://doi.org/10.1007/s00401-010-0678-x

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TDP-43 pathology in sporadic ALS occurs in motor neurons lacking the RNA editing enzyme ADAR2

Abstract

Keynote webinar | Spotlight on medication adherence

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Abstract

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