臨床神経学

<シンポジウム(2)―2―2>ALSの病態進行機序の新展開

TDP-43のシード依存的細胞内凝集体形成

野中 隆, 長谷川 成人

東京都医学総合研究所・認知症プロジェクト〔〒156―8506 東京都世田谷区上北沢2―1―6〕

TAR-DNA binding protein of 43 kDa (TDP-43) is the component protein of inclusions in brains of patients with frontotemporal lobar degeneration (FTLD-TDP) and amyotrophic lateral sclerosis (ALS). Here we report a seed-dependent TDP-43 aggregation model using SH-SY5Y cells into which detergent-insoluble TDP-43 from diseased brains is introduced to provide seeds for aggregation. When these seeds were introduced into cells expressing HA-tagged TDP-43, round aggregates composed of phosphorylated and ubiquitinated HA-tagged TDP-43 were formed. Biochemical fractionation revealed the presence of Sarkosyl-insoluble phosphorylated full-length TDP-43 as well as its C-terminal fragments. Cells bearing TDP-43 inclusions exhibited increased levels of cell death and proteasome dysfunction. This seeding model reproduces characteristic features of affected neurons in brains with TDP-43 proteinopathy.
Full Text of this Article in Japanese PDF (216K)

(臨床神経, 52:1056−1058, 2012)
key words:前頭側頭葉変性症,筋萎縮性側索硬化症,TDP-43,伝播,シード依存的凝集体形成

(受付日:2012年5月24日)