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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Autores principales: Keiji Uchiyama, Hideyuki Hara, Junji Chida, Agriani Dini Pasiana, Morikazu Imamura, Tsuyoshi Mori, Hanae Takatsuki, Ryuichiro Atarashi, Suehiro Sakaguchi
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Publicado: MDPI AG 2021
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Acceso en línea:https://doaj.org/article/9ee846da524b4800b896217172b50898
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spelling oai:doaj.org-article:9ee846da524b4800b896217172b508982021-11-11T17:11:57ZEthanolamine Is a New Anti-Prion Compound10.3390/ijms2221117421422-00671661-6596https://doaj.org/article/9ee846da524b4800b896217172b508982021-10-01T00:00:00Zhttps://www.mdpi.com/1422-0067/22/21/11742https://doaj.org/toc/1661-6596https://doaj.org/toc/1422-0067Prion 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.Keiji UchiyamaHideyuki HaraJunji ChidaAgriani Dini PasianaMorikazu ImamuraTsuyoshi MoriHanae TakatsukiRyuichiro AtarashiSuehiro SakaguchiMDPI AGarticleprionsprion proteinprotein misfoldingneurodegenerationethanolaminetherapyBiology (General)QH301-705.5ChemistryQD1-999ENInternational Journal of Molecular Sciences, Vol 22, Iss 11742, p 11742 (2021)
institution DOAJ
collection DOAJ
language EN
topic prions
prion protein
protein misfolding
neurodegeneration
ethanolamine
therapy
Biology (General)
QH301-705.5
Chemistry
QD1-999
spellingShingle prions
prion protein
protein misfolding
neurodegeneration
ethanolamine
therapy
Biology (General)
QH301-705.5
Chemistry
QD1-999
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
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.
format article
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
title Ethanolamine Is a New Anti-Prion Compound
title_short 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_sort ethanolamine is a new anti-prion compound
publisher MDPI AG
publishDate 2021
url https://doaj.org/article/9ee846da524b4800b896217172b50898
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
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