mTOR in Alzheimer disease and its earlier stages: Links to oxidative damage in the progression of this dementing disorder.
mTOR in Alzheimer disease and its earlier stages: Links to oxidative damage in the progression of this dementing disorder.
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阿尔茨海默病及其早期阶段的mTOR：与这种痴呆症进展中的氧化损伤有关
DOI：
10.1016/j.freeradbiomed.2021.04.025
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发表时间：
2021-06
影响因子：
7.4
通讯作者：
Butterfield DA
中科院分区：
文献类型：
--
作者：
Perluigi M;Di Domenico F;Barone E;Butterfield DA
阿尔茨海默病(AD)是老年人群中最常见的痴呆症，具有世界性影响。该病的病因很复杂，是多种机制汇合的结果，最终导致神经元丧失和认知能力下降。在风险因素中，衰老是最相关的，并解释了几种致病事件，这些事件有助于疾病特有的毒性机制。越来越多的证据表明，哺乳动物靶标雷帕霉素(MTOR)的变化与年龄相关性认知能力下降和AD的发病机制有关。雷帕霉素是一种丝氨酸/苏氨酸蛋白激酶，在蛋白质合成和降解过程中发挥关键作用。到目前为止，越来越多的研究表明，大脑中异常的mTOR信号影响着能量代谢、细胞生长、线粒体功能和蛋白平衡等几个途径。最近的研究进展表明，mTOR途径的改变与氧化应激的增加有关。所有这些事件的中断都强烈地导致了包括阿尔茨海默病在内的与年龄相关的认知下降。本文讨论了mTOR信号网络在大脑中的主要调节作用，重点讨论了它在自噬、氧化应激和能量代谢中的作用。总而言之，实验数据表明，靶向中枢神经系统的mTOR可能是预防/减缓AD进展的一个有价值的策略。
Alzheimer’s disease (AD) is the most prevalent form of dementia in the elderly population and has worldwide impact. The etiology of the disease is complex and results from the confluence of multiple mechanisms ultimately leading to neuronal loss and cognitive decline. Among risk factors, aging is the most relevant and accounts for several pathogenic events that contribute to disease-specific toxic mechanisms. Accumulating evidence linked the alterations of the mammalian target of rapamycin (mTOR), a serine/threonine protein kinase playing a key role in the regulation of protein synthesis and degradation, to age-dependent cognitive decline and pathogenesis of AD. To date, growing studies demonstrated that aberrant mTOR signaling in the brain affects several pathways involved in energy metabolism, cell growth, mitochondrial function and proteostasis. Recent advances associated alterations of the mTOR pathway with the increased oxidative stress. Disruption of all these events strongly contribute to age-related cognitive decline including AD. The current review discusses the main regulatory roles of mTOR signaling network in the brain, focusing on its role in autophagy, oxidative stress and energy metabolism. Collectively, experimental data suggest that targeting mTOR in the CNS can be a valuable strategy to prevent/slow the progression of AD.
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DOI：
10.1038/nrneurol.2017.185
发表时间：
2018-03
期刊：
Nature reviews. Neurology
影响因子：
--
作者：
Arnold SE;Arvanitakis Z;Macauley-Rambach SL;Koenig AM;Wang HY;Ahima RS;Craft S;Gandy S;Buettner C;Stoeckel LE;Holtzman DM;Nathan DM
通讯作者：
Nathan DM
影响因子：
6.1
作者：
Aluise CD;Robinson RA;Beckett TL;Murphy MP;Cai J;Pierce WM;Markesbery WR;Butterfield DA
通讯作者：
Butterfield DA
神经元中的自噬诱导和自噬体清除：与阿尔茨海默氏病自噬病理学的关系。
影响因子：
5.3
作者：
Boland, Barry;Kumar, Asok;Lee, Sooyeon;Platt, Frances M.;Wegiel, Jerzy;Yu, W. Haung;Nixon, Ralph A.
通讯作者：
Nixon, Ralph A.
影响因子：
2.5
作者：
Butterfield, DA;Reed, T;Sultana, R
通讯作者：
Sultana, R
影响因子：
4.7
作者：
Bilsland, Lynsey G.;Nirmalananthan, Niranjanan;Duchen, Michael R.
通讯作者：
Duchen, Michael R.