Ganglioside Synthase Knockout Reduces Prion Disease Incubation Time in Mouse Models

Atsushi Kobayashi, Zechen Qi, Taishi Shimazaki, Yoshiko Munesue, Tomomi Miyamoto, Norikazu Isoda, Hirofumi Sawa, Keisuke Aoshima, Takashi Kimura, Shirou Mohri, Tetsuyuki Kitamoto, Tadashi Yamashita, Ichiro Miyoshi

Research output: Contribution to journalArticle

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-Sträussler-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.

Original languageEnglish
Pages (from-to)677-686
Number of pages10
JournalAmerican Journal of Pathology
Volume189
Issue number3
DOIs
Publication statusPublished - 2019 Mar

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Fingerprint Dive into the research topics of 'Ganglioside Synthase Knockout Reduces Prion Disease Incubation Time in Mouse Models'. Together they form a unique fingerprint.

  • Cite this

    Kobayashi, A., Qi, Z., Shimazaki, T., Munesue, Y., Miyamoto, T., Isoda, N., Sawa, H., Aoshima, K., Kimura, T., Mohri, S., Kitamoto, T., Yamashita, T., & Miyoshi, I. (2019). Ganglioside Synthase Knockout Reduces Prion Disease Incubation Time in Mouse Models. American Journal of Pathology, 189(3), 677-686. https://doi.org/10.1016/j.ajpath.2018.11.009