Cerebral mTOR signal and pro-inflammatory cytokines in Alzheimer’s disease rats

As a part of Alzheimer’s disease (AD) development the mammalian target of rapamycin (mTOR) has been reported to play a crucial role in regulating cognition and can be used as a neuronal marker. Neuro-inflammation is also a cause of the pathophysiological process in AD. Thus, we examined the protein...

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Autores principales:	Wang Xu, Li Guang-Jian, Hu Hai-Xia, Ma Chi, Ma Di-Hui, Liu Xiao-Liang, Jiang Xiao-Ming
Formato:	article
Lenguaje:	EN
Publicado:	De Gruyter 2016
Materias:	alzheimer’s disease caspase-3 hippocampus mammalian target of rapamycin (mtor) pro-inflammatory cytokines Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571
Acceso en línea:	https://doaj.org/article/7014cd78adb44dbb938e073dc8f38040
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spelling	oai:doaj.org-article:7014cd78adb44dbb938e073dc8f380402021-12-05T14:11:04ZCerebral mTOR signal and pro-inflammatory cytokines in Alzheimer’s disease rats2081-693610.1515/tnsci-2016-0022https://doaj.org/article/7014cd78adb44dbb938e073dc8f380402016-01-01T00:00:00Zhttps://doi.org/10.1515/tnsci-2016-0022https://doaj.org/toc/2081-6936As a part of Alzheimer’s disease (AD) development the mammalian target of rapamycin (mTOR) has been reported to play a crucial role in regulating cognition and can be used as a neuronal marker. Neuro-inflammation is also a cause of the pathophysiological process in AD. Thus, we examined the protein expression levels of mTOR and its downstream pathways as well as pro-inflammatory cytokines (PICs) in the brain of AD rats. We further examined the effects of blocking mTOR on PICs, namely IL-1β, IL-6 and TNF-α. Our results showed that the protein expression of p-mTOR, mTOR-mediated phosphorylation of 4E-binding protein 4 (4E-BP1) and p70 ribosomal S6 protein kinase 1 (S6K1) pathways were amplified in the hippocampus of AD rats compared with controls. Blocking mTOR by using rapamycin selectively enhanced activities of IL-6 and TNF-α signaling pathways, which was accompanied with an increase of Caspase-3, indicating cellular apoptosis and worsened learning performance. In conclusion, our data for the first time revealed specific signaling pathways engaged in the development of AD, including a regulatory role by the activation of mTOR in PIC mechanisms. Stimulation of mTOR is likely to play a beneficial role in modulating neurological deficits in AD.Targeting one or more of these signaling molecules may present with new opportunities for treatment and clinical management of ADWang XuLi Guang-JianHu Hai-XiaMa ChiMa Di-HuiLiu Xiao-LiangJiang Xiao-MingDe Gruyterarticlealzheimer’s diseasecaspase-3hippocampusmammalian target of rapamycin (mtor)pro-inflammatory cytokinesNeurosciences. Biological psychiatry. NeuropsychiatryRC321-571ENTranslational Neuroscience, Vol 7, Iss 1, Pp 151-157 (2016)
institution	DOAJ
collection	DOAJ
language	EN
topic	alzheimer’s disease caspase-3 hippocampus mammalian target of rapamycin (mtor) pro-inflammatory cytokines Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571
spellingShingle	alzheimer’s disease caspase-3 hippocampus mammalian target of rapamycin (mtor) pro-inflammatory cytokines Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571 Wang Xu Li Guang-Jian Hu Hai-Xia Ma Chi Ma Di-Hui Liu Xiao-Liang Jiang Xiao-Ming Cerebral mTOR signal and pro-inflammatory cytokines in Alzheimer’s disease rats
description	As a part of Alzheimer’s disease (AD) development the mammalian target of rapamycin (mTOR) has been reported to play a crucial role in regulating cognition and can be used as a neuronal marker. Neuro-inflammation is also a cause of the pathophysiological process in AD. Thus, we examined the protein expression levels of mTOR and its downstream pathways as well as pro-inflammatory cytokines (PICs) in the brain of AD rats. We further examined the effects of blocking mTOR on PICs, namely IL-1β, IL-6 and TNF-α. Our results showed that the protein expression of p-mTOR, mTOR-mediated phosphorylation of 4E-binding protein 4 (4E-BP1) and p70 ribosomal S6 protein kinase 1 (S6K1) pathways were amplified in the hippocampus of AD rats compared with controls. Blocking mTOR by using rapamycin selectively enhanced activities of IL-6 and TNF-α signaling pathways, which was accompanied with an increase of Caspase-3, indicating cellular apoptosis and worsened learning performance. In conclusion, our data for the first time revealed specific signaling pathways engaged in the development of AD, including a regulatory role by the activation of mTOR in PIC mechanisms. Stimulation of mTOR is likely to play a beneficial role in modulating neurological deficits in AD.Targeting one or more of these signaling molecules may present with new opportunities for treatment and clinical management of AD
format	article
author	Wang Xu Li Guang-Jian Hu Hai-Xia Ma Chi Ma Di-Hui Liu Xiao-Liang Jiang Xiao-Ming
author_facet	Wang Xu Li Guang-Jian Hu Hai-Xia Ma Chi Ma Di-Hui Liu Xiao-Liang Jiang Xiao-Ming
author_sort	Wang Xu
title	Cerebral mTOR signal and pro-inflammatory cytokines in Alzheimer’s disease rats
title_short	Cerebral mTOR signal and pro-inflammatory cytokines in Alzheimer’s disease rats
title_full	Cerebral mTOR signal and pro-inflammatory cytokines in Alzheimer’s disease rats
title_fullStr	Cerebral mTOR signal and pro-inflammatory cytokines in Alzheimer’s disease rats
title_full_unstemmed	Cerebral mTOR signal and pro-inflammatory cytokines in Alzheimer’s disease rats
title_sort	cerebral mtor signal and pro-inflammatory cytokines in alzheimer’s disease rats
publisher	De Gruyter
publishDate	2016
url	https://doaj.org/article/7014cd78adb44dbb938e073dc8f38040
work_keys_str_mv	AT wangxu cerebralmtorsignalandproinflammatorycytokinesinalzheimersdiseaserats AT liguangjian cerebralmtorsignalandproinflammatorycytokinesinalzheimersdiseaserats AT huhaixia cerebralmtorsignalandproinflammatorycytokinesinalzheimersdiseaserats AT machi cerebralmtorsignalandproinflammatorycytokinesinalzheimersdiseaserats AT madihui cerebralmtorsignalandproinflammatorycytokinesinalzheimersdiseaserats AT liuxiaoliang cerebralmtorsignalandproinflammatorycytokinesinalzheimersdiseaserats AT jiangxiaoming cerebralmtorsignalandproinflammatorycytokinesinalzheimersdiseaserats
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Cerebral mTOR signal and pro-inflammatory cytokines in Alzheimer’s disease rats

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