Ganglioside Synthase Knockout Reduces Prion Disease Incubation Time in Mouse Models

Kobayashi, Atsushi; Qi, Zechen; Shimazaki, Taishi et al.

The American Journal of Pathology, 2019, 189(3), 677-686

Permalink : https://hdl.handle.net/2115/76315

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アクセス権
open access
URI
https://hdl.handle.net/2115/76315
タイトル
Ganglioside Synthase Knockout Reduces Prion Disease Incubation Time in Mouse Models
著者
Kobayashi, Atsushi ; Qi, Zechen ; Shimazaki, Taishi ; Munesue, Yoshiko ; Miyamoto, Tomomi ; Isoda, Norikazu ; Sawa, Hirofumi ; Aoshima, Keisuke ; Kimura, Takashi ; Mohri, Shirou ; Kitamoto, Tetsuyuki ; Yamashita, Tadashi ; Miyoshi, Ichiro
著者名
Kobayashi, Atsushi
著者名
Qi, Zechen
著者名
Shimazaki, Taishi
著者名
Munesue, Yoshiko
著者名
Miyamoto, Tomomi
著者名
Isoda, Norikazu
著者名
Sawa, Hirofumi
著者名
Aoshima, Keisuke
著者名
Kimura, Takashi
著者名
Mohri, Shirou
著者名
Kitamoto, Tetsuyuki
著者名
Yamashita, Tadashi
著者名
Miyoshi, Ichiro
言語
英語
発行日
2019-03
出版者
Elsevier
収録物名
The American Journal of Pathology
巻(号)
189(3)
ページ
677-686
抄録
Localization of the abnormal and normal isoforms of prion proteins to detergent-resistant membrane microdomains, lipid rafts, is important for the conformational conversion. Lipid rafts are enriched in sialic acid-containing glycosphingolipids (namely, gangliosides). Alteration in the ganglioside composition of lipid rafts can affect the localization of lipid raft-associated proteins. To investigate the role of gangliosides in the pathogenesis of prion diseases, we performed intracerebral transmission study of a scrapie prion strain Chandler and a Gerstmann-Straussler-Scheinker syndrome prion strain Fukuoka-1 using various knockout mouse strains ablated with ganglioside synthase gene (ie, GD2/GM2 synthase, GD3 synthase, or GM3 synthase). After challenge with the Chandler strain, GD2/GM2 synthase knockout mice showed 20% reduction of incubation time, reduced prion protein deposition in the brain with attenuated glial reactions, and reduced localization of prion proteins to lipid rafts. These results raise the possibility that the gangliosides may have an important role in prion disease pathogenesis by affecting the localization of prion proteins to lipid rafts.
資源タイプ
学術雑誌論文
出版タイプ
Accepted Manuscript
権利情報
Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International
権利情報
©2019, Elsevier. Licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International http://creativecommons.org/licenses/by-nc-nd/4.0/
PISSN
0002-9440
関連情報 (isVersionOf)
出版社版DOI
https://doi.org/10.1016/j.ajpath.2018.11.009