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

PURPOSE: 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 protein...

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Autores principales: Gao, Jie, Chen, Xiaohan, Ma, Tianjun, He, Bin, Li, Peng, Zhao, Yucheng, Ma, Yuejin, Zhuang, Jianhua, Yin, You
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Dove 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7494393/
https://www.ncbi.nlm.nih.gov/pubmed/32982233
http://dx.doi.org/10.2147/IJN.S258311
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author Gao, Jie
Chen, Xiaohan
Ma, Tianjun
He, Bin
Li, Peng
Zhao, Yucheng
Ma, Yuejin
Zhuang, Jianhua
Yin, You
author_facet Gao, Jie
Chen, Xiaohan
Ma, Tianjun
He, Bin
Li, Peng
Zhao, Yucheng
Ma, Yuejin
Zhuang, Jianhua
Yin, You
author_sort Gao, Jie
collection PubMed
description PURPOSE: 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.
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spelling pubmed-74943932020-09-24 PEG-Ceramide Nanomicelles Induce Autophagy and Degrade Tau Proteins in N2a Cells Gao, Jie Chen, Xiaohan Ma, Tianjun He, Bin Li, Peng Zhao, Yucheng Ma, Yuejin Zhuang, Jianhua Yin, You Int J Nanomedicine Original Research PURPOSE: 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. Dove 2020-09-11 /pmc/articles/PMC7494393/ /pubmed/32982233 http://dx.doi.org/10.2147/IJN.S258311 Text en © 2020 Gao et al. http://creativecommons.org/licenses/by-nc/3.0/ This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License (http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms (https://www.dovepress.com/terms.php).
spellingShingle Original Research
Gao, Jie
Chen, Xiaohan
Ma, Tianjun
He, Bin
Li, Peng
Zhao, Yucheng
Ma, Yuejin
Zhuang, Jianhua
Yin, You
PEG-Ceramide Nanomicelles Induce Autophagy and Degrade Tau Proteins in N2a Cells
title 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_short 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
topic Original Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7494393/
https://www.ncbi.nlm.nih.gov/pubmed/32982233
http://dx.doi.org/10.2147/IJN.S258311
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