ID 112431
著者
Ogawa, Yasuhiro Meiji Pharmaceutical University
Sano, Takafumi Meiji Pharmaceutical University
Irisa, Masahiro Meiji Pharmaceutical University
Kodama, Takashi Meiji Pharmaceutical University
Saito, Takahiro Meiji Pharmaceutical University
Furusawa, Eiri Meiji Pharmaceutical University
Kaizu, Katsutoshi Meiji Pharmaceutical University
Yanagi, Yusuke Meiji Pharmaceutical University
Tsukimura, Takahiro Meiji Pharmaceutical University
Togawa, Tadayasu Meiji Pharmaceutical University
Yamanaka, Shoji Yokohama City University
Sakuraba, Hitoshi Meiji Pharmaceutical University
Oishi, Kazuhiko Meiji Pharmaceutical University
資料タイプ
学術雑誌論文
抄録
Sandhoff disease (SD) is caused by the loss of β-hexosaminidase (Hex) enzymatic activity in lysosomes resulting from Hexb mutations. In SD patients, the Hex substrate GM2 ganglioside accumulates abnormally in neuronal cells, resulting in neuronal loss, microglial activation, and astrogliosis. Hexb−/− mice, which manifest a phenotype similar to SD, serve as animal models for examining the pathophysiology of SD. Hexb−/− mice reach ~8 weeks without obvious neurological defects; however, trembling begins at 12 weeks and is accompanied by startle reactions and increased limb tone. These symptoms gradually become severe by 16–18 weeks. Immune reactions caused by autoantibodies have been recently associated with the pathology of SD. The inhibition of immune activation may represent a novel therapeutic target for SD. Herein, SD mice (Hexb−/−) were crossed to mice lacking an activating immune receptor (FcRγ−/−) to elucidate the potential relationship between immune responses activated through SD autoantibodies and astrogliosis. Microglial activation and astrogliosis were observed in cortices of Hexb−/− mice during the asymptomatic phase, and were inhibited in Hexb−/− FcRγ−/− mice. Moreover, early astrogliosis and impaired motor coordination in Hexb−/− mice could be ameliorated by immunosuppressants, such as FTY720. Our findings demonstrate the importance of early treatment and the therapeutic effectiveness of immunosuppression in SD.
掲載誌名
Scientific Reports
ISSN
20452322
出版者
Springer Nature
7
開始ページ
40518
発行日
2017-01-13
備考
Supplementary Information : srep_7_40518_s1.pdf
権利情報
© The Author(s) 2017
This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
EDB ID
339728
出版社版DOI
出版社版URL
フルテキストファイル
言語
eng
著者版フラグ
出版社版
部局
薬学系