Ethanolamine Is a New Anti-Prion Compound
Prion diseases are a group of fatal neurodegenerative disorders caused by accumulation of proteinaceous infectious particles, or prions, which mainly consist of the abnormally folded, amyloidogenic prion protein, designated PrP<sup>Sc</sup>. PrP<sup>Sc</sup> is produced throu...
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2021-10-01
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author | Keiji Uchiyama Hideyuki Hara Junji Chida Agriani Dini Pasiana Morikazu Imamura Tsuyoshi Mori Hanae Takatsuki Ryuichiro Atarashi Suehiro Sakaguchi |
author_facet | Keiji Uchiyama Hideyuki Hara Junji Chida Agriani Dini Pasiana Morikazu Imamura Tsuyoshi Mori Hanae Takatsuki Ryuichiro Atarashi Suehiro Sakaguchi |
author_sort | Keiji Uchiyama |
collection | DOAJ |
description | Prion diseases are a group of fatal neurodegenerative disorders caused by accumulation of proteinaceous infectious particles, or prions, which mainly consist of the abnormally folded, amyloidogenic prion protein, designated PrP<sup>Sc</sup>. PrP<sup>Sc</sup> is produced through conformational conversion of the cellular isoform of prion protein, PrP<sup>C</sup>, in the brain. To date, no effective therapies for prion diseases have been developed. In this study, we incidentally noticed that mouse neuroblastoma N2a cells persistently infected with 22L scrapie prions, termed N2aC24L1-3 cells, reduced PrP<sup>Sc</sup> levels when cultured in advanced Dulbecco’s modified eagle medium (DMEM) but not in classic DMEM. PrP<sup>C</sup> levels remained unchanged in prion-uninfected parent N2aC24 cells cultured in advanced DMEM. These results suggest that advanced DMEM may contain an anti-prion compound(s). We then successfully identified ethanolamine in advanced DMEM has an anti-prion activity. Ethanolamine reduced PrP<sup>Sc</sup> levels in N2aC24L1-3 cells, but not PrP<sup>C</sup> levels in N2aC24 cells. Also, oral administration of ethanolamine through drinking water delayed prion disease in mice intracerebrally inoculated with RML scrapie prions. These results suggest that ethanolamine could be a new anti-prion compound. |
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spelling | doaj.art-9ee846da524b4800b896217172b508982023-11-22T20:57:09ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-10-0122211174210.3390/ijms222111742Ethanolamine Is a New Anti-Prion CompoundKeiji Uchiyama0Hideyuki Hara1Junji Chida2Agriani Dini Pasiana3Morikazu Imamura4Tsuyoshi Mori5Hanae Takatsuki6Ryuichiro Atarashi7Suehiro Sakaguchi8Division of Molecular Neurobiology, The Institute for Enzyme Research (KOSOKEN), Tokushima University, 3-18-15 Kuramoto, Tokushima 770-8503, JapanDivision of Molecular Neurobiology, The Institute for Enzyme Research (KOSOKEN), Tokushima University, 3-18-15 Kuramoto, Tokushima 770-8503, JapanDivision of Molecular Neurobiology, The Institute for Enzyme Research (KOSOKEN), Tokushima University, 3-18-15 Kuramoto, Tokushima 770-8503, JapanDivision of Molecular Neurobiology, The Institute for Enzyme Research (KOSOKEN), Tokushima University, 3-18-15 Kuramoto, Tokushima 770-8503, JapanDivision of Microbiology, Department of Infectious Diseases, Faculty of Medicine, University of Miyazaki, 5200 Kihara, Kiyotake, Miyazaki 889-1692, JapanDivision of Microbiology, Department of Infectious Diseases, Faculty of Medicine, University of Miyazaki, 5200 Kihara, Kiyotake, Miyazaki 889-1692, JapanDivision of Microbiology, Department of Infectious Diseases, Faculty of Medicine, University of Miyazaki, 5200 Kihara, Kiyotake, Miyazaki 889-1692, JapanDivision of Microbiology, Department of Infectious Diseases, Faculty of Medicine, University of Miyazaki, 5200 Kihara, Kiyotake, Miyazaki 889-1692, JapanDivision of Molecular Neurobiology, The Institute for Enzyme Research (KOSOKEN), Tokushima University, 3-18-15 Kuramoto, Tokushima 770-8503, JapanPrion diseases are a group of fatal neurodegenerative disorders caused by accumulation of proteinaceous infectious particles, or prions, which mainly consist of the abnormally folded, amyloidogenic prion protein, designated PrP<sup>Sc</sup>. PrP<sup>Sc</sup> is produced through conformational conversion of the cellular isoform of prion protein, PrP<sup>C</sup>, in the brain. To date, no effective therapies for prion diseases have been developed. In this study, we incidentally noticed that mouse neuroblastoma N2a cells persistently infected with 22L scrapie prions, termed N2aC24L1-3 cells, reduced PrP<sup>Sc</sup> levels when cultured in advanced Dulbecco’s modified eagle medium (DMEM) but not in classic DMEM. PrP<sup>C</sup> levels remained unchanged in prion-uninfected parent N2aC24 cells cultured in advanced DMEM. These results suggest that advanced DMEM may contain an anti-prion compound(s). We then successfully identified ethanolamine in advanced DMEM has an anti-prion activity. Ethanolamine reduced PrP<sup>Sc</sup> levels in N2aC24L1-3 cells, but not PrP<sup>C</sup> levels in N2aC24 cells. Also, oral administration of ethanolamine through drinking water delayed prion disease in mice intracerebrally inoculated with RML scrapie prions. These results suggest that ethanolamine could be a new anti-prion compound.https://www.mdpi.com/1422-0067/22/21/11742prionsprion proteinprotein misfoldingneurodegenerationethanolaminetherapy |
spellingShingle | Keiji Uchiyama Hideyuki Hara Junji Chida Agriani Dini Pasiana Morikazu Imamura Tsuyoshi Mori Hanae Takatsuki Ryuichiro Atarashi Suehiro Sakaguchi Ethanolamine Is a New Anti-Prion Compound International Journal of Molecular Sciences prions prion protein protein misfolding neurodegeneration ethanolamine therapy |
title | Ethanolamine Is a New Anti-Prion Compound |
title_full | Ethanolamine Is a New Anti-Prion Compound |
title_fullStr | Ethanolamine Is a New Anti-Prion Compound |
title_full_unstemmed | Ethanolamine Is a New Anti-Prion Compound |
title_short | Ethanolamine Is a New Anti-Prion Compound |
title_sort | ethanolamine is a new anti prion compound |
topic | prions prion protein protein misfolding neurodegeneration ethanolamine therapy |
url | https://www.mdpi.com/1422-0067/22/21/11742 |
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