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Activation of mTOR: a culprit of Alzheimer’s disease?

Alzheimer’s disease (AD) is characterized by cognitive impairment in clinical presentation, and by β-amyloid (Aβ) production and the hyper-phosphorylation of tau in basic research. More highlights demonstrate that the activation of the mammalian target of rapamycin (mTOR) enhances Aβ generation and...

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Autores principales: Cai, Zhiyou, Chen, Guanghui, He, Wenbo, Xiao, Ming, Yan, Liang-Jun
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Dove Medical Press 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4399516/
https://www.ncbi.nlm.nih.gov/pubmed/25914534
http://dx.doi.org/10.2147/NDT.S75717
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author Cai, Zhiyou
Chen, Guanghui
He, Wenbo
Xiao, Ming
Yan, Liang-Jun
author_facet Cai, Zhiyou
Chen, Guanghui
He, Wenbo
Xiao, Ming
Yan, Liang-Jun
author_sort Cai, Zhiyou
collection PubMed
description Alzheimer’s disease (AD) is characterized by cognitive impairment in clinical presentation, and by β-amyloid (Aβ) production and the hyper-phosphorylation of tau in basic research. More highlights demonstrate that the activation of the mammalian target of rapamycin (mTOR) enhances Aβ generation and deposition by modulating amyloid precursor protein (APP) metabolism and upregulating β- and γ-secretases. mTOR, an inhibitor of autophagy, decreases Aβ clearance by scissoring autophagy function. mTOR regulates Aβ generation or Aβ clearance by regulating several key signaling pathways, including phosphoinositide 3-kinase (PI3-K)/protein kinase B (Akt), glycogen synthase kinase 3 [GSK-3], AMP-activated protein kinase (AMPK), and insulin/insulin-like growth factor 1 (IGF-1). The activation of mTOR is also a contributor to aberrant hyperphosphorylated tau. Rapamycin, the inhibitor of mTOR, may mitigate cognitive impairment and inhibit the pathologies associated with amyloid plaques and neurofibrillary tangles by promoting autophagy. Furthermore, the upstream and downstream components of mTOR signaling are involved in the pathogenesis and progression of AD. Hence, inhibiting the activation of mTOR may be an important therapeutic target for AD.
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spelling pubmed-43995162015-04-24 Activation of mTOR: a culprit of Alzheimer’s disease? Cai, Zhiyou Chen, Guanghui He, Wenbo Xiao, Ming Yan, Liang-Jun Neuropsychiatr Dis Treat Review Alzheimer’s disease (AD) is characterized by cognitive impairment in clinical presentation, and by β-amyloid (Aβ) production and the hyper-phosphorylation of tau in basic research. More highlights demonstrate that the activation of the mammalian target of rapamycin (mTOR) enhances Aβ generation and deposition by modulating amyloid precursor protein (APP) metabolism and upregulating β- and γ-secretases. mTOR, an inhibitor of autophagy, decreases Aβ clearance by scissoring autophagy function. mTOR regulates Aβ generation or Aβ clearance by regulating several key signaling pathways, including phosphoinositide 3-kinase (PI3-K)/protein kinase B (Akt), glycogen synthase kinase 3 [GSK-3], AMP-activated protein kinase (AMPK), and insulin/insulin-like growth factor 1 (IGF-1). The activation of mTOR is also a contributor to aberrant hyperphosphorylated tau. Rapamycin, the inhibitor of mTOR, may mitigate cognitive impairment and inhibit the pathologies associated with amyloid plaques and neurofibrillary tangles by promoting autophagy. Furthermore, the upstream and downstream components of mTOR signaling are involved in the pathogenesis and progression of AD. Hence, inhibiting the activation of mTOR may be an important therapeutic target for AD. Dove Medical Press 2015-04-09 /pmc/articles/PMC4399516/ /pubmed/25914534 http://dx.doi.org/10.2147/NDT.S75717 Text en © 2015 Cai et al. This work is published by Dove Medical Press Limited, and licensed under Creative Commons Attribution – Non Commercial (unported, v3.0) License The full terms of the License are available at http://creativecommons.org/licenses/by-nc/3.0/. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed.
spellingShingle Review
Cai, Zhiyou
Chen, Guanghui
He, Wenbo
Xiao, Ming
Yan, Liang-Jun
Activation of mTOR: a culprit of Alzheimer’s disease?
title Activation of mTOR: a culprit of Alzheimer’s disease?
title_full Activation of mTOR: a culprit of Alzheimer’s disease?
title_fullStr Activation of mTOR: a culprit of Alzheimer’s disease?
title_full_unstemmed Activation of mTOR: a culprit of Alzheimer’s disease?
title_short Activation of mTOR: a culprit of Alzheimer’s disease?
title_sort activation of mtor: a culprit of alzheimer’s disease?
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4399516/
https://www.ncbi.nlm.nih.gov/pubmed/25914534
http://dx.doi.org/10.2147/NDT.S75717
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