Isoform-Specific Effects of Apolipoprotein E on Hydrogen Peroxide-Induced Apoptosis in Human Induced Pluripotent Stem Cell (iPSC)-Derived Cortical Neurons

Hydrogen peroxide (H<sub>2</sub>O<sub>2</sub>)-induced neuronal apoptosis is critical to the pathology of Alzheimer’s disease (AD) as well as other neurodegenerative diseases. The neuroprotective effects of apolipoprotein (ApoE) isoforms against apoptosis and the underlying m...

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Autores principales:	Huiling Gao, Wei Zheng, Cheng Li, He Xu
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	apolipoprotein E apoptosis iPSC-derived cortical neurons Alzheimer’s disease neurodegeneration Biology (General) QH301-705.5 Chemistry QD1-999
Acceso en línea:	https://doaj.org/article/38aa761eb4964c3a902c1977c308c2fe
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spelling	oai:doaj.org-article:38aa761eb4964c3a902c1977c308c2fe2021-11-11T17:03:59ZIsoform-Specific Effects of Apolipoprotein E on Hydrogen Peroxide-Induced Apoptosis in Human Induced Pluripotent Stem Cell (iPSC)-Derived Cortical Neurons10.3390/ijms2221115821422-00671661-6596https://doaj.org/article/38aa761eb4964c3a902c1977c308c2fe2021-10-01T00:00:00Zhttps://www.mdpi.com/1422-0067/22/21/11582https://doaj.org/toc/1661-6596https://doaj.org/toc/1422-0067Hydrogen peroxide (H<sub>2</sub>O<sub>2</sub>)-induced neuronal apoptosis is critical to the pathology of Alzheimer’s disease (AD) as well as other neurodegenerative diseases. The neuroprotective effects of apolipoprotein (ApoE) isoforms against apoptosis and the underlying mechanism remains controversial. Here, we have generated human cortical neurons from iPSCs and induced apoptosis with H<sub>2</sub>O<sub>2</sub>. We show that ApoE2 and ApoE3 pretreatments significantly attenuate neuronal apoptosis, whereas ApoE4 has no neuroprotective effect and higher concentrations of ApoE4 even display toxic effect. We further identify that ApoE2 and ApoE3 regulate Akt/FoxO3a/Bim signaling pathway in the presence of H<sub>2</sub>O<sub>2</sub>. We propose that ApoE alleviates H<sub>2</sub>O<sub>2</sub>-induced apoptosis in human iPSC-derived neuronal culture in an isoform specific manner. Our results provide an alternative mechanistic explanation on how ApoE isoforms influence the risk of AD onset as well as a promising therapeutic target for diseases involving neuronal apoptosis in the central nervous system.Huiling GaoWei ZhengCheng LiHe XuMDPI AGarticleapolipoprotein EapoptosisiPSC-derived cortical neuronsAlzheimer’s diseaseneurodegenerationBiology (General)QH301-705.5ChemistryQD1-999ENInternational Journal of Molecular Sciences, Vol 22, Iss 11582, p 11582 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	apolipoprotein E apoptosis iPSC-derived cortical neurons Alzheimer’s disease neurodegeneration Biology (General) QH301-705.5 Chemistry QD1-999
spellingShingle	apolipoprotein E apoptosis iPSC-derived cortical neurons Alzheimer’s disease neurodegeneration Biology (General) QH301-705.5 Chemistry QD1-999 Huiling Gao Wei Zheng Cheng Li He Xu Isoform-Specific Effects of Apolipoprotein E on Hydrogen Peroxide-Induced Apoptosis in Human Induced Pluripotent Stem Cell (iPSC)-Derived Cortical Neurons
description	Hydrogen peroxide (H<sub>2</sub>O<sub>2</sub>)-induced neuronal apoptosis is critical to the pathology of Alzheimer’s disease (AD) as well as other neurodegenerative diseases. The neuroprotective effects of apolipoprotein (ApoE) isoforms against apoptosis and the underlying mechanism remains controversial. Here, we have generated human cortical neurons from iPSCs and induced apoptosis with H<sub>2</sub>O<sub>2</sub>. We show that ApoE2 and ApoE3 pretreatments significantly attenuate neuronal apoptosis, whereas ApoE4 has no neuroprotective effect and higher concentrations of ApoE4 even display toxic effect. We further identify that ApoE2 and ApoE3 regulate Akt/FoxO3a/Bim signaling pathway in the presence of H<sub>2</sub>O<sub>2</sub>. We propose that ApoE alleviates H<sub>2</sub>O<sub>2</sub>-induced apoptosis in human iPSC-derived neuronal culture in an isoform specific manner. Our results provide an alternative mechanistic explanation on how ApoE isoforms influence the risk of AD onset as well as a promising therapeutic target for diseases involving neuronal apoptosis in the central nervous system.
format	article
author	Huiling Gao Wei Zheng Cheng Li He Xu
author_facet	Huiling Gao Wei Zheng Cheng Li He Xu
author_sort	Huiling Gao
title	Isoform-Specific Effects of Apolipoprotein E on Hydrogen Peroxide-Induced Apoptosis in Human Induced Pluripotent Stem Cell (iPSC)-Derived Cortical Neurons
title_short	Isoform-Specific Effects of Apolipoprotein E on Hydrogen Peroxide-Induced Apoptosis in Human Induced Pluripotent Stem Cell (iPSC)-Derived Cortical Neurons
title_full	Isoform-Specific Effects of Apolipoprotein E on Hydrogen Peroxide-Induced Apoptosis in Human Induced Pluripotent Stem Cell (iPSC)-Derived Cortical Neurons
title_fullStr	Isoform-Specific Effects of Apolipoprotein E on Hydrogen Peroxide-Induced Apoptosis in Human Induced Pluripotent Stem Cell (iPSC)-Derived Cortical Neurons
title_full_unstemmed	Isoform-Specific Effects of Apolipoprotein E on Hydrogen Peroxide-Induced Apoptosis in Human Induced Pluripotent Stem Cell (iPSC)-Derived Cortical Neurons
title_sort	isoform-specific effects of apolipoprotein e on hydrogen peroxide-induced apoptosis in human induced pluripotent stem cell (ipsc)-derived cortical neurons
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/38aa761eb4964c3a902c1977c308c2fe
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Isoform-Specific Effects of Apolipoprotein E on Hydrogen Peroxide-Induced Apoptosis in Human Induced Pluripotent Stem Cell (iPSC)-Derived Cortical Neurons

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