PEG-Ceramide Nanomicelles Induce Autophagy and Degrade Tau Proteins in N2a Cells

Jie Gao,1,2,* Xiaohan Chen,1,* Tianjun Ma,1,* Bin He,1 Peng Li,1 Yucheng Zhao,1 Yuejin Ma,1 Jianhua Zhuang,1 You Yin1 1Department of Neurology, Changzheng Hospital, Second Military Medical University, Shanghai 200003, People’s Republic of China; 2Institute of Translational Medicine, Shangh...

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Autores principales:	Gao J, Chen X, Ma T, He B, Li P, Zhao Y, Ma Y, Zhuang J, Yin Y
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2020
Materias:	alzheimer's disease autophagosomes lysosome nano-carrier autophagic flux Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/bbf838e1fb114c10add448ee80e36cb4
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spelling	oai:doaj.org-article:bbf838e1fb114c10add448ee80e36cb42021-12-02T12:59:34ZPEG-Ceramide Nanomicelles Induce Autophagy and Degrade Tau Proteins in N2a Cells1178-2013https://doaj.org/article/bbf838e1fb114c10add448ee80e36cb42020-09-01T00:00:00Zhttps://www.dovepress.com/peg-ceramide-nanomicelles-induce-autophagy-and-degrade-tau-proteins-in-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Jie Gao,1,2,* Xiaohan Chen,1,* Tianjun Ma,1,* Bin He,1 Peng Li,1 Yucheng Zhao,1 Yuejin Ma,1 Jianhua Zhuang,1 You Yin1 1Department of Neurology, Changzheng Hospital, Second Military Medical University, Shanghai 200003, People’s Republic of China; 2Institute of Translational Medicine, Shanghai University, Shanghai 200444, People’s Republic of China*These authors contributed equally to this workCorrespondence: You Yin; Jianhua ZhuangDepartment of Neurology, Changzheng Hospital, Second Military Medical University, Shanghai 200003, People’s Republic of ChinaTel/Fax +86-21-63586818Email yinyou179@163.com; jianhuazh11@126.comPurpose: Alzheimer’s disease (AD) is a neurodegenerative disorder that manifests as abnormal behavior and a progressive decline in memory. Although the pathogenesis of AD is due to the excessive deposition of amyloid β protein (Aβ) outside the neurons in the brain, evidence suggests that tau proteins may be a better target for AD therapy. In neurodegenerative diseases, a decrease in autophagy results in the failure to eliminate abnormally deposited or misfolded proteins. Therefore, induction of autophagy may be an effective way to eliminate tau proteins in the treatment of AD. We investigated the effects of polyethylene glycol (PEG)-ceramide nanomicelles on autophagy and on tau proteins in N2a, a murine neuroblastoma metrocyte cell line.Methods: Ceramide is a sphingolipid bioactive molecule that induces autophagy. PEG-ceramide is a polymer that is composed of the hydrophobic chain of ceramide and the hydrophilic chain of PEG-2000. In this study, we prepared PEG-ceramide nanomicelles that were 10– 20 nm in size and had nearly neutral zeta potential.Results: The results show that PEG-ceramide nanomicelles caused an increase in the LC3-II/LC3-I ratio, while p62 protein levels decreased. Confocal microscopy revealed a significant increase in the number of dots corresponding to autophagosomes and autolysosomes, which indicated autophagic activation. Moreover, PEG-ceramide nanomicelles induced tau degradation in N2a cells through autophagy.Conclusion: In summary, we have confirmed that PEG-ceramide nanomicelles enhanced autophagic flux and degraded overexpressed human tau proteins in N2a cells by regulating the autophagy pathway. Thus, PEG-ceramide nanomicelles show great promise as agents to induce autophagy and degrade tau proteins in the treatment of AD.Keywords: Alzheimer’s disease, autophagosomes, lysosome, nano-carrier, autophagic fluxGao JChen XMa THe BLi PZhao YMa YZhuang JYin YDove Medical Pressarticlealzheimer's diseaseautophagosomeslysosomenano-carrierautophagic fluxMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 15, Pp 6779-6789 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	alzheimer's disease autophagosomes lysosome nano-carrier autophagic flux Medicine (General) R5-920
spellingShingle	alzheimer's disease autophagosomes lysosome nano-carrier autophagic flux Medicine (General) R5-920 Gao J Chen X Ma T He B Li P Zhao Y Ma Y Zhuang J Yin Y PEG-Ceramide Nanomicelles Induce Autophagy and Degrade Tau Proteins in N2a Cells
description	Jie Gao,1,2,* Xiaohan Chen,1,* Tianjun Ma,1,* Bin He,1 Peng Li,1 Yucheng Zhao,1 Yuejin Ma,1 Jianhua Zhuang,1 You Yin1 1Department of Neurology, Changzheng Hospital, Second Military Medical University, Shanghai 200003, People’s Republic of China; 2Institute of Translational Medicine, Shanghai University, Shanghai 200444, People’s Republic of China*These authors contributed equally to this workCorrespondence: You Yin; Jianhua ZhuangDepartment of Neurology, Changzheng Hospital, Second Military Medical University, Shanghai 200003, People’s Republic of ChinaTel/Fax +86-21-63586818Email yinyou179@163.com; jianhuazh11@126.comPurpose: Alzheimer’s disease (AD) is a neurodegenerative disorder that manifests as abnormal behavior and a progressive decline in memory. Although the pathogenesis of AD is due to the excessive deposition of amyloid β protein (Aβ) outside the neurons in the brain, evidence suggests that tau proteins may be a better target for AD therapy. In neurodegenerative diseases, a decrease in autophagy results in the failure to eliminate abnormally deposited or misfolded proteins. Therefore, induction of autophagy may be an effective way to eliminate tau proteins in the treatment of AD. We investigated the effects of polyethylene glycol (PEG)-ceramide nanomicelles on autophagy and on tau proteins in N2a, a murine neuroblastoma metrocyte cell line.Methods: Ceramide is a sphingolipid bioactive molecule that induces autophagy. PEG-ceramide is a polymer that is composed of the hydrophobic chain of ceramide and the hydrophilic chain of PEG-2000. In this study, we prepared PEG-ceramide nanomicelles that were 10– 20 nm in size and had nearly neutral zeta potential.Results: The results show that PEG-ceramide nanomicelles caused an increase in the LC3-II/LC3-I ratio, while p62 protein levels decreased. Confocal microscopy revealed a significant increase in the number of dots corresponding to autophagosomes and autolysosomes, which indicated autophagic activation. Moreover, PEG-ceramide nanomicelles induced tau degradation in N2a cells through autophagy.Conclusion: In summary, we have confirmed that PEG-ceramide nanomicelles enhanced autophagic flux and degraded overexpressed human tau proteins in N2a cells by regulating the autophagy pathway. Thus, PEG-ceramide nanomicelles show great promise as agents to induce autophagy and degrade tau proteins in the treatment of AD.Keywords: Alzheimer’s disease, autophagosomes, lysosome, nano-carrier, autophagic flux
format	article
author	Gao J Chen X Ma T He B Li P Zhao Y Ma Y Zhuang J Yin Y
author_facet	Gao J Chen X Ma T He B Li P Zhao Y Ma Y Zhuang J Yin Y
author_sort	Gao J
title	PEG-Ceramide Nanomicelles Induce Autophagy and Degrade Tau Proteins in N2a Cells
title_short	PEG-Ceramide Nanomicelles Induce Autophagy and Degrade Tau Proteins in N2a Cells
title_full	PEG-Ceramide Nanomicelles Induce Autophagy and Degrade Tau Proteins in N2a Cells
title_fullStr	PEG-Ceramide Nanomicelles Induce Autophagy and Degrade Tau Proteins in N2a Cells
title_full_unstemmed	PEG-Ceramide Nanomicelles Induce Autophagy and Degrade Tau Proteins in N2a Cells
title_sort	peg-ceramide nanomicelles induce autophagy and degrade tau proteins in n2a cells
publisher	Dove Medical Press
publishDate	2020
url	https://doaj.org/article/bbf838e1fb114c10add448ee80e36cb4
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PEG-Ceramide Nanomicelles Induce Autophagy and Degrade Tau Proteins in N2a Cells

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