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j.stemcr.2017.12.001.pdf | 7.15 MB | Adobe 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 https://orcid.org/0000-0002-6251-0810 (unconfirmed) Ayaki, Takashi Kawamoto, Yasuhiro Furuta, Takahiro Urushitani, Makoto Hasegawa, Masato Kinoshita, Yusuke Ono, Yuichi Mao, Xiaobo Quach, Tran H. Iwai, Kazuhiro https://orcid.org/0000-0001-5620-5951 (unconfirmed) Dawson, Valina L. Dawson, Ted M. Takahashi, Ryosuke https://orcid.org/0000-0002-1407-9640 (unconfirmed) |
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: | Feb-2018 |
出版者: | Elsevier BV |
誌名: | Stem Cell Reports |
巻: | 10 |
号: | 2 |
開始ページ: | 356 |
終了ページ: | 365 |
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 |
PubMed ID: | 29337114 |
関連リンク: | https://www.kyoto-u.ac.jp/ja/research-news/2018-01-12 |
出現コレクション: | 学術雑誌掲載論文等 |
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