N-Acetylcysteine prevents amyloid-β secretion in neurons derived from human pluripotent stem cells with trisomy 21

Abstract Down syndrome (DS) is caused by the trisomy of chromosome 21. Among the many disabilities found in individuals with DS is an increased risk of early-onset Alzheimer's disease (AD). Although higher oxidative stress and an upregulation of amyloid β (Aβ) peptides from an extra copy of the...

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Autores principales:	Hiromitsu Toshikawa, Akihiro Ikenaka, Li Li, Yoko Nishinaka-Arai, Akira Niwa, Akira Ashida, Yasuhiro Kazuki, Tatsutoshi Nakahata, Hiroshi Tamai, David W. Russell, Megumu K. Saito
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/f6ec21f457ad44418f46ddc15d05fa8e
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spelling	oai:doaj.org-article:f6ec21f457ad44418f46ddc15d05fa8e2021-12-02T15:29:03ZN-Acetylcysteine prevents amyloid-β secretion in neurons derived from human pluripotent stem cells with trisomy 2110.1038/s41598-021-96697-72045-2322https://doaj.org/article/f6ec21f457ad44418f46ddc15d05fa8e2021-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-96697-7https://doaj.org/toc/2045-2322Abstract Down syndrome (DS) is caused by the trisomy of chromosome 21. Among the many disabilities found in individuals with DS is an increased risk of early-onset Alzheimer's disease (AD). Although higher oxidative stress and an upregulation of amyloid β (Aβ) peptides from an extra copy of the APP gene are attributed to the AD susceptibility, the relationship between the two factors is unclear. To address this issue, we established an in vitro cellular model using neurons differentiated from DS patient-derived induced pluripotent stem cells (iPSCs) and isogenic euploid iPSCs. Neurons differentiated from DS patient-derived iPSCs secreted more Aβ compared to those differentiated from the euploid iPSCs. Treatment of the neurons with an antioxidant, N-acetylcysteine, significantly suppressed the Aβ secretion. These findings suggest that oxidative stress has an important role in controlling the Aβ level in neurons differentiated from DS patient-derived iPSCs and that N-acetylcysteine can be a potential therapeutic option to ameliorate the Aβ secretion.Hiromitsu ToshikawaAkihiro IkenakaLi LiYoko Nishinaka-AraiAkira NiwaAkira AshidaYasuhiro KazukiTatsutoshi NakahataHiroshi TamaiDavid W. RussellMegumu K. SaitoNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-10 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Hiromitsu Toshikawa Akihiro Ikenaka Li Li Yoko Nishinaka-Arai Akira Niwa Akira Ashida Yasuhiro Kazuki Tatsutoshi Nakahata Hiroshi Tamai David W. Russell Megumu K. Saito N-Acetylcysteine prevents amyloid-β secretion in neurons derived from human pluripotent stem cells with trisomy 21
description	Abstract Down syndrome (DS) is caused by the trisomy of chromosome 21. Among the many disabilities found in individuals with DS is an increased risk of early-onset Alzheimer's disease (AD). Although higher oxidative stress and an upregulation of amyloid β (Aβ) peptides from an extra copy of the APP gene are attributed to the AD susceptibility, the relationship between the two factors is unclear. To address this issue, we established an in vitro cellular model using neurons differentiated from DS patient-derived induced pluripotent stem cells (iPSCs) and isogenic euploid iPSCs. Neurons differentiated from DS patient-derived iPSCs secreted more Aβ compared to those differentiated from the euploid iPSCs. Treatment of the neurons with an antioxidant, N-acetylcysteine, significantly suppressed the Aβ secretion. These findings suggest that oxidative stress has an important role in controlling the Aβ level in neurons differentiated from DS patient-derived iPSCs and that N-acetylcysteine can be a potential therapeutic option to ameliorate the Aβ secretion.
format	article
author	Hiromitsu Toshikawa Akihiro Ikenaka Li Li Yoko Nishinaka-Arai Akira Niwa Akira Ashida Yasuhiro Kazuki Tatsutoshi Nakahata Hiroshi Tamai David W. Russell Megumu K. Saito
author_facet	Hiromitsu Toshikawa Akihiro Ikenaka Li Li Yoko Nishinaka-Arai Akira Niwa Akira Ashida Yasuhiro Kazuki Tatsutoshi Nakahata Hiroshi Tamai David W. Russell Megumu K. Saito
author_sort	Hiromitsu Toshikawa
title	N-Acetylcysteine prevents amyloid-β secretion in neurons derived from human pluripotent stem cells with trisomy 21
title_short	N-Acetylcysteine prevents amyloid-β secretion in neurons derived from human pluripotent stem cells with trisomy 21
title_full	N-Acetylcysteine prevents amyloid-β secretion in neurons derived from human pluripotent stem cells with trisomy 21
title_fullStr	N-Acetylcysteine prevents amyloid-β secretion in neurons derived from human pluripotent stem cells with trisomy 21
title_full_unstemmed	N-Acetylcysteine prevents amyloid-β secretion in neurons derived from human pluripotent stem cells with trisomy 21
title_sort	n-acetylcysteine prevents amyloid-β secretion in neurons derived from human pluripotent stem cells with trisomy 21
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/f6ec21f457ad44418f46ddc15d05fa8e
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N-Acetylcysteine prevents amyloid-β secretion in neurons derived from human pluripotent stem cells with trisomy 21

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