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The Pluripotency Factor Nanog Protects against Neuronal Amyloid β-Induced Toxicity and Oxidative Stress through Insulin Sensitivity Restoration

Amyloid β (Aβ) is a peptide fragment of the amyloid precursor protein that triggers the progression of Alzheimer’s Disease (AD). It is believed that Aβ contributes to neurodegeneration in several ways, including mitochondria dysfunction, oxidative stress and brain insulin resistance. Therefore, prot...

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Autores principales: Chang, Ching-Chi, Li, Hsin-Hua, Tsou, Sing-Hua, Hung, Hui-Chih, Liu, Guang-Yaw, Korolenko, Tatiana A., Lai, Te-Jen, Ho, Ying-Jui, Lin, Chih-Li
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7348813/
https://www.ncbi.nlm.nih.gov/pubmed/32471175
http://dx.doi.org/10.3390/cells9061339
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author Chang, Ching-Chi
Li, Hsin-Hua
Tsou, Sing-Hua
Hung, Hui-Chih
Liu, Guang-Yaw
Korolenko, Tatiana A.
Lai, Te-Jen
Ho, Ying-Jui
Lin, Chih-Li
author_facet Chang, Ching-Chi
Li, Hsin-Hua
Tsou, Sing-Hua
Hung, Hui-Chih
Liu, Guang-Yaw
Korolenko, Tatiana A.
Lai, Te-Jen
Ho, Ying-Jui
Lin, Chih-Li
author_sort Chang, Ching-Chi
collection PubMed
description Amyloid β (Aβ) is a peptide fragment of the amyloid precursor protein that triggers the progression of Alzheimer’s Disease (AD). It is believed that Aβ contributes to neurodegeneration in several ways, including mitochondria dysfunction, oxidative stress and brain insulin resistance. Therefore, protecting neurons from Aβ-induced neurotoxicity is an effective strategy for attenuating AD pathogenesis. Recently, applications of stem cell-based therapies have demonstrated the ability to reduce the progression and outcome of neurodegenerative diseases. Particularly, Nanog is recognized as a stem cell-related pluripotency factor that enhances self-renewing capacities and helps reduce the senescent phenotypes of aged neuronal cells. However, whether the upregulation of Nanog can be an effective approach to alleviate Aβ-induced neurotoxicity and senescence is not yet understood. In the present study, we transiently overexpressed Nanog—both in vitro and in vivo—and investigated the protective effects and underlying mechanisms against Aβ. We found that overexpression of Nanog is responsible for attenuating Aβ-triggered neuronal insulin resistance, which restores cell survival through reducing intracellular mitochondrial superoxide accumulation and cellular senescence. In addition, upregulation of Nanog expression appears to increase secretion of neurotrophic factors through activation of the Nrf2 antioxidant defense pathway. Furthermore, improvement of memory and learning were also observed in rat model of Aβ neurotoxicity mediated by upregulation of Nanog in the brain. Taken together, our study suggests a potential role for Nanog in attenuating the neurotoxic effects of Aβ, which in turn, suggests that strategies to enhance Nanog expression may be used as a novel intervention for reducing Aβ neurotoxicity in the AD brain.
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spelling pubmed-73488132020-07-22 The Pluripotency Factor Nanog Protects against Neuronal Amyloid β-Induced Toxicity and Oxidative Stress through Insulin Sensitivity Restoration Chang, Ching-Chi Li, Hsin-Hua Tsou, Sing-Hua Hung, Hui-Chih Liu, Guang-Yaw Korolenko, Tatiana A. Lai, Te-Jen Ho, Ying-Jui Lin, Chih-Li Cells Article Amyloid β (Aβ) is a peptide fragment of the amyloid precursor protein that triggers the progression of Alzheimer’s Disease (AD). It is believed that Aβ contributes to neurodegeneration in several ways, including mitochondria dysfunction, oxidative stress and brain insulin resistance. Therefore, protecting neurons from Aβ-induced neurotoxicity is an effective strategy for attenuating AD pathogenesis. Recently, applications of stem cell-based therapies have demonstrated the ability to reduce the progression and outcome of neurodegenerative diseases. Particularly, Nanog is recognized as a stem cell-related pluripotency factor that enhances self-renewing capacities and helps reduce the senescent phenotypes of aged neuronal cells. However, whether the upregulation of Nanog can be an effective approach to alleviate Aβ-induced neurotoxicity and senescence is not yet understood. In the present study, we transiently overexpressed Nanog—both in vitro and in vivo—and investigated the protective effects and underlying mechanisms against Aβ. We found that overexpression of Nanog is responsible for attenuating Aβ-triggered neuronal insulin resistance, which restores cell survival through reducing intracellular mitochondrial superoxide accumulation and cellular senescence. In addition, upregulation of Nanog expression appears to increase secretion of neurotrophic factors through activation of the Nrf2 antioxidant defense pathway. Furthermore, improvement of memory and learning were also observed in rat model of Aβ neurotoxicity mediated by upregulation of Nanog in the brain. Taken together, our study suggests a potential role for Nanog in attenuating the neurotoxic effects of Aβ, which in turn, suggests that strategies to enhance Nanog expression may be used as a novel intervention for reducing Aβ neurotoxicity in the AD brain. MDPI 2020-05-27 /pmc/articles/PMC7348813/ /pubmed/32471175 http://dx.doi.org/10.3390/cells9061339 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Chang, Ching-Chi
Li, Hsin-Hua
Tsou, Sing-Hua
Hung, Hui-Chih
Liu, Guang-Yaw
Korolenko, Tatiana A.
Lai, Te-Jen
Ho, Ying-Jui
Lin, Chih-Li
The Pluripotency Factor Nanog Protects against Neuronal Amyloid β-Induced Toxicity and Oxidative Stress through Insulin Sensitivity Restoration
title The Pluripotency Factor Nanog Protects against Neuronal Amyloid β-Induced Toxicity and Oxidative Stress through Insulin Sensitivity Restoration
title_full The Pluripotency Factor Nanog Protects against Neuronal Amyloid β-Induced Toxicity and Oxidative Stress through Insulin Sensitivity Restoration
title_fullStr The Pluripotency Factor Nanog Protects against Neuronal Amyloid β-Induced Toxicity and Oxidative Stress through Insulin Sensitivity Restoration
title_full_unstemmed The Pluripotency Factor Nanog Protects against Neuronal Amyloid β-Induced Toxicity and Oxidative Stress through Insulin Sensitivity Restoration
title_short The Pluripotency Factor Nanog Protects against Neuronal Amyloid β-Induced Toxicity and Oxidative Stress through Insulin Sensitivity Restoration
title_sort pluripotency factor nanog protects against neuronal amyloid β-induced toxicity and oxidative stress through insulin sensitivity restoration
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7348813/
https://www.ncbi.nlm.nih.gov/pubmed/32471175
http://dx.doi.org/10.3390/cells9061339
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