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ID 117387
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
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
Springer Nature
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University Hospital
Medical Sciences