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j.stemcr.2017.12.001.pdf7.15 MBAdobe PDF見る/開く
タイトル: Pathological Endogenous α-Synuclein Accumulation in Oligodendrocyte Precursor Cells Potentially Induces Inclusions in Multiple System Atrophy
著者: Kaji, Seiji
Maki, Takakuni
Kinoshita, Hisanori
Uemura, Norihito
Ayaki, Takashi
Kawamoto, Yasuhiro
Furuta, Takahiro
Urushitani, Makoto
Hasegawa, Masato
Kinoshita, Yusuke
Ono, Yuichi
Mao, Xiaobo
Quach, Tran H.
Iwai, Kazuhiro
Dawson, Valina L.
Dawson, Ted M.
Takahashi, Ryosuke
著者名の別形: 梶, 誠兒
眞木, 崇州
木下, 久徳
上村, 紀仁
綾木, 孝
河本, 恭裕
古田, 貴寛
漆谷, 真
長谷川, 成人
木下, 裕介
尾野, 雄一
岩井, 一宏
高橋, 良輔
キーワード: α-synuclein
oligodendrocytes
oligodendrocyte precursor cells
primary cell culture
multiple system atrophy
synucleinopathy
glial cytoplasmic inclusion
neurotrophic factor
misfolding
autophagy
発行日: 11-Jan-2018
出版者: Elsevier BV
誌名: Stem Cell Reports
抄録: Glial cytoplasmic inclusions (GCIs), commonly observed as α-synuclein (α-syn)-positive aggregates within oligodendrocytes, are the pathological hallmark of multiple system atrophy. The origin of α-syn in GCIs is uncertain; there is little evidence of endogenous α-syn expression in oligodendrocyte lineage cells, oligodendrocyte precursor cells (OPCs), and mature oligodendrocytes (OLGs). Here, based on in vitro analysis using primary rat cell cultures, we elucidated that preformed fibrils (PFFs) generated from recombinant human α-syn trigger multimerization and an upsurge of endogenous α-syn in OPCs, which is attributable to insufficient autophagic proteolysis. RNA-seq analysis of OPCs revealed that α-syn PFFs interfered with the expression of proteins associated with neuromodulation and myelination. Furthermore, we detected cytoplasmic α-syn inclusions in OLGs through differentiation of OPCs pre-incubated with PFFs. Overall, our findings suggest the possibility of endogenous α-syn accumulation in OPCs that contributes to GCI formation and perturbation of neuronal/glial support in multiple system atrophy brains.
記述: 神経難病である多系統萎縮症の細胞内封入体形成メカニズムを一部解明 --病態解明と治療法開発に向けた細胞モデルの樹立--. 京都大学プレスリリース. 2018-01-12.
著作権等: © 2017 The Author(s). This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
URI: http://hdl.handle.net/2433/228877
DOI(出版社版): 10.1016/j.stemcr.2017.12.001
関連リンク: http://www.kyoto-u.ac.jp/ja/research/research_results/2017/180112_1.html
出現コレクション:学術雑誌掲載論文等

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