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ID 117387
Author
Egawa, Naohiro Kyoto University|RIKEN
Suzuki, Hidefumi Kyoto University|RIKEN
Tsuge, Itaru Kyoto University
Shimano, Hitoshi University of Tsukuba
Izumikawa, Keiichi Tokyo University of Agriculture and Technology
Takahashi, Nobuhiro Tokyo University of Agriculture and Technology
Tsukita, Kayoko Kyoto University|RIKEN
Enami, Takako Kyoto University|RIKEN
Nakamura, Masahiro Kyoto University
Watanabe, Akira Kyoto University
Naitoh, Motoko Kyoto University
Suzuki, Shigehiko Kyoto University
Seki, Tsuneyoshi Kobe University
Kobayashi, Kazuhiro Kobe University
Toda, Tatsushi Kobe University|The University of Tokyo
Takahashi, Ryosuke Kyoto University
Inoue, Haruhisa Kyoto University|RIKEN
Content Type
Journal Article
Description
Dyslipidemia is considered an essential component of the pathological process of amyotrophic lateral sclerosis (ALS), a fatal motor neuron disease. Although TAR DNA Binding Protein 43 kDa (TDP-43) links both familial and sporadic forms of ALS and cytoplasmic aggregates are a hallmark of most cases of ALS, the molecular mechanism and the in vivo relation of ALS dyslipidemia with TDP-43 have been unclear. To analyze the dyslipidemia-related gene expression by TDP-43, we performed expression microarray and RNA deep sequencing (RNA-Seq) using cell lines expressing high levels of TDP-43 and identified 434 significantly altered genes including sterol regulatory element-binding protein 2 (SREBP2), a master regulator of cholesterol homeostasis and its downstream genes. Elevated TDP-43 impaired SREBP2 transcriptional activity, leading to inhibition of cholesterol biosynthesis. The amount of cholesterol was significantly decreased in the spinal cords of TDP-43-overexpressed ALS model mice and in the cerebrospinal fluids of ALS patients. These results suggested that TDP-43 could play an essential role in cholesterol biosynthesis in relation to ALS dyslipidemia.
Journal Title
Scientific Reports
ISSN
20452322
Publisher
Springer Nature
Volume
12
Start Page
7988
Published Date
2022-05-14
Rights
This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.
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language
eng
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departments
University Hospital
Medical Sciences