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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Main Authors: Keiji Uchiyama, Hideyuki Hara, Junji Chida, Agriani Dini Pasiana, Morikazu Imamura, Tsuyoshi Mori, Hanae Takatsuki, Ryuichiro Atarashi, Suehiro Sakaguchi
Format: Article
Language:English
Published: MDPI AG 2021-10-01
Series:International Journal of Molecular Sciences
Subjects:
Online Access:https://www.mdpi.com/1422-0067/22/21/11742
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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
work_keys_str_mv AT keijiuchiyama ethanolamineisanewantiprioncompound
AT hideyukihara ethanolamineisanewantiprioncompound
AT junjichida ethanolamineisanewantiprioncompound
AT agrianidinipasiana ethanolamineisanewantiprioncompound
AT morikazuimamura ethanolamineisanewantiprioncompound
AT tsuyoshimori ethanolamineisanewantiprioncompound
AT hanaetakatsuki ethanolamineisanewantiprioncompound
AT ryuichiroatarashi ethanolamineisanewantiprioncompound
AT suehirosakaguchi ethanolamineisanewantiprioncompound