| Title: | Ganglioside Synthase Knockout Reduces Prion Disease Incubation Time in Mouse Models |
| Authors: | Kobayashi, Atsushi Browse this author |
| Qi, Zechen Browse this author |
| Shimazaki, Taishi Browse this author |
| Munesue, Yoshiko Browse this author |
| Miyamoto, Tomomi Browse this author |
| Isoda, Norikazu Browse this author |
| Sawa, Hirofumi Browse this author |
| Aoshima, Keisuke Browse this author |
| Kimura, Takashi Browse this author |
| Mohri, Shirou Browse this author |
| Kitamoto, Tetsuyuki Browse this author |
| Yamashita, Tadashi Browse this author |
| Miyoshi, Ichiro Browse this author |
| Issue Date: | Mar-2019 |
| Publisher: | Elsevier |
| Journal Title: | The American Journal of Pathology |
| Volume: | 189 |
| Issue: | 3 |
| Start Page: | 677 |
| End Page: | 686 |
| Publisher DOI: | 10.1016/j.ajpath.2018.11.009 |
| Abstract: | 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. |
| Rights: | ©2019, Elsevier. Licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International http://creativecommons.org/licenses/by-nc-nd/4.0/ |
| http://creativecommons.org/licenses/by-nc-nd/4.0/ |
| Type: | article (author version) |
| URI: | http://hdl.handle.net/2115/76315 |
| Appears in Collections: | 獣医学院・獣医学研究院 (Graduate School of Veterinary Medicine / Faculty of Veterinary Medicine) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)
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