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本文引用的文献

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Cardiovascular disease and mTOR signaling.心血管疾病与 mTOR 信号通路。
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2
The interaction between early life epilepsy and autistic-like behavioral consequences: a role for the mammalian target of rapamycin (mTOR) pathway.早期癫痫与类似自闭症行为后果之间的相互作用:哺乳动物雷帕霉素靶蛋白(mTOR)途径的作用。
PLoS One. 2012;7(5):e35885. doi: 10.1371/journal.pone.0035885. Epub 2012 May 2.
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Metformin preconditioning protects Daphnia pulex from lethal hypoxic insult involving AMPK, HIF and mTOR signaling.二甲双胍预处理可保护溞属(水蚤)免受涉及 AMPK、HIF 和 mTOR 信号通路的致死性缺氧损伤。
Comp Biochem Physiol B Biochem Mol Biol. 2012 Sep;163(1):51-8. doi: 10.1016/j.cbpb.2012.04.009. Epub 2012 May 4.
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Rapamycin attenuates aggressive behavior in a rat model of pilocarpine-induced epilepsy.雷帕霉素可减轻匹鲁卡品诱导癫痫大鼠的攻击行为。
Neuroscience. 2012 Jul 26;215:90-7. doi: 10.1016/j.neuroscience.2012.04.011. Epub 2012 Apr 20.
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The many facets of cell injury: angiogenesis to autophagy.细胞损伤的多个方面:从血管生成到自噬
Curr Neurovasc Res. 2012 May;9(2):83-4. doi: 10.2174/156720212800410911.
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WISP1 (CCN4) autoregulates its expression and nuclear trafficking of β-catenin during oxidant stress with limited effects upon neuronal autophagy.在氧化应激条件下,WISP1(CCN4)通过自调控其表达和β-catenin 的核转位,对神经元自噬的影响有限。
Curr Neurovasc Res. 2012 May;9(2):91-101. doi: 10.2174/156720212800410858.
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Autophagy induced by resveratrol prevents human prion protein-mediated neurotoxicity.白藜芦醇诱导的自噬可预防人朊病毒蛋白介导的神经毒性。
Neurosci Res. 2012 Jun;73(2):99-105. doi: 10.1016/j.neures.2012.03.005. Epub 2012 Mar 23.
8
Inhibition of protein tyrosine phosphatase improves angiogenesis via enhancing Ang-1/Tie-2 signaling in diabetes.抑制蛋白酪氨酸磷酸酶可通过增强糖尿病中的血管生成素-1/酪氨酸激酶受体2信号传导来改善血管生成。
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NVP-BEZ235 and NVP-BGT226, dual phosphatidylinositol 3-kinase/mammalian target of rapamycin inhibitors, enhance tumor and endothelial cell radiosensitivity.NVP-BEZ235 和 NVP-BGT226 是双重磷脂酰肌醇 3-激酶/雷帕霉素哺乳动物靶蛋白抑制剂,可增强肿瘤和内皮细胞的放射敏感性。
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Erythropoiesis-stimulating agent administration and survival after severe traumatic brain injury: a prospective study.严重创伤性脑损伤后促红细胞生成素刺激剂的使用与生存情况:一项前瞻性研究
Arch Surg. 2012 Mar;147(3):251-5. doi: 10.1001/archsurg.2011.1838.

通过哺乳动物雷帕霉素靶蛋白揭示神经退行性疾病的新曙光。

Shedding new light on neurodegenerative diseases through the mammalian target of rapamycin.

机构信息

Laboratory of Cellular and Molecular Signaling, Cancer Center, F 1220, New Jersey Health Sciences University, 205 South Orange Avenue, Newark, NJ 07101, USA.

出版信息

Prog Neurobiol. 2012 Nov;99(2):128-48. doi: 10.1016/j.pneurobio.2012.08.001. Epub 2012 Aug 15.

DOI:10.1016/j.pneurobio.2012.08.001
PMID:22980037
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3479314/
Abstract

Neurodegenerative disorders affect a significant portion of the world's population leading to either disability or death for almost 30 million individuals worldwide. One novel therapeutic target that may offer promise for multiple disease entities that involve Alzheimer's disease, Parkinson's disease, epilepsy, trauma, stroke, and tumors of the nervous system is the mammalian target of rapamycin (mTOR). mTOR signaling is dependent upon the mTORC1 and mTORC2 complexes that are composed of mTOR and several regulatory proteins including the tuberous sclerosis complex (TSC1, hamartin/TSC2, tuberin). Through a number of integrated cell signaling pathways that involve those of mTORC1 and mTORC2 as well as more novel signaling tied to cytokines, Wnt, and forkhead, mTOR can foster stem cellular proliferation, tissue repair and longevity, and synaptic growth by modulating mechanisms that foster both apoptosis and autophagy. Yet, mTOR through its proliferative capacity may sometimes be detrimental to central nervous system recovery and even promote tumorigenesis. Further knowledge of mTOR and the critical pathways governed by this serine/threonine protein kinase can bring new light for neurodegeneration and other related diseases that currently require new and robust treatments.

摘要

神经退行性疾病影响了世界上相当一部分人口,导致全球近 3000 万人残疾或死亡。哺乳动物雷帕霉素靶蛋白(mTOR)是一种新型治疗靶点,可能对涉及阿尔茨海默病、帕金森病、癫痫、创伤、中风和神经系统肿瘤的多种疾病实体具有治疗潜力。mTOR 信号通路依赖于 mTORC1 和 mTORC2 复合物,该复合物由 mTOR 和几种调节蛋白组成,包括结节性硬化复合物(TSC1、错构瘤/TSC2、结节性硬化症)。通过涉及 mTORC1 和 mTORC2 的许多整合细胞信号通路以及与细胞因子、Wnt 和叉头相关的更新型信号通路,mTOR 可以通过调节促进凋亡和自噬的机制,促进干细胞增殖、组织修复和长寿以及突触生长。然而,mTOR 通过其增殖能力有时可能对中枢神经系统的恢复有害,甚至促进肿瘤发生。进一步了解 mTOR 及其丝氨酸/苏氨酸蛋白激酶调控的关键途径,可以为神经退行性疾病和其他目前需要新的和强大治疗方法的相关疾病带来新的启示。