Energy metabolism and inflammation in brain aging and Alzheimer's disease.
Energy metabolism and inflammation in brain aging and Alzheimer's disease.
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DOI：
10.1016/j.freeradbiomed.2016.04.200
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发表时间：
2016-11
影响因子：
7.4
通讯作者：
Cadenas, Enrique
中科院分区：
文献类型：
--
作者：
Yin, Fei;Sancheti, Harsh;Patil, Ishan;Cadenas, Enrique
大脑的高能量需求使其对能量燃料供应和线粒体功能的变化敏感。葡萄糖可用性和线粒体功能的缺陷是脑老化的众所周知的标志，并且在神经退行性疾病如阿尔茨海默病中特别突出。作为H2O2的重要细胞来源，线粒体功能障碍通常与氧化还原状态的改变有关。生物能量缺陷和慢性氧化应激都是与脑老化和阿尔茨海默病相关的认知能力下降的主要原因。在神经退行性疾病和正常衰老中观察到神经炎性变化，包括小胶质细胞活化和炎性细胞因子的产生。生物能量假说主张从代谢缺陷到神经元功能障碍的传播、到衰老和到神经变性的连续事件，而炎症假说支持小胶质细胞活化作为神经炎症的驱动力。然而，越来越多的证据表明，这些不同的机制有氧化还原失调作为一个共同的分母和连接器。大脑老化和神经退行性变机制的独立观点正在被一种需要多种机制相互协调和相互作用的观点所取代。本文综述了正常脑老化和阿尔茨海默病中能量代谢和炎症反应的改变及其通过氧化还原调节的联系。基于基础研究和临床研究，这些系统的相互作用进行了综述。
The high energy demand of the brain renders it sensitive to changes in energy fuel supply and mitochondrial function. Deficits in glucose availability and mitochondrial function are well-known hallmarks of brain aging and are particularly accentuated in neurodegenerative disorders such as Alzheimer’s disease. As important cellular sources of H2O2, mitochondrial dysfunction is usually associated with altered redox status. Bioenergetic deficits and chronic oxidative stress are both major contributors to cognitive decline associated with brain aging and Alzheimer’s disease. Neuroinflammatory changes, including microglial activation and production of inflammatory cytokines, are observed in neurodegenerative diseases and normal aging. The bioenergetic hypothesis advocates for sequential events from metabolic deficits to propagation of neuronal dysfunction, to aging, and to neurodegeneration, while the inflammatory hypothesis supports microglia activation as the driving force for neuroinflammation. Nevertheless, growing evidence suggests that these diverse mechanisms have redox dysregulation as a common denominator and connector. An independent view of the mechanisms underlying brain aging and neurodegeneration is being replaced by one that entails multiple mechanisms coordinating and interacting with each other. This review focuses on the alterations in energy metabolism and inflammatory responses and their connection via redox regulation in normal brain aging and Alzheimer’s disease. Interactions of these systems is reviewed based on basic research and clinical studies.
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影响因子：
7.4
作者：
Bruce-Keller, Annadora J.;White, Christy L.;Gupta, Sunita;Knight, Alecia G.;Pistell, Paul J.;Ingram, Donald K.;Morrison, Christopher D.;Keller, Jeffrey N.
通讯作者：
Keller, Jeffrey N.
DOI：
10.1152/ajplung.00219.2012
发表时间：
2012-11-01
影响因子：
4.9
作者：
Agarwal, Amit R.;Zhao, Liqin;Cadenas, Enrique
通讯作者：
Cadenas, Enrique
影响因子：
17.7
作者：
Alexander, GE;Chen, K;Reiman, EM
通讯作者：
Reiman, EM
影响因子：
3.9
作者：
CADENAS, E;BOVERIS, A;STOPPANI, AOM
通讯作者：
STOPPANI, AOM
DOI：
10.1016/j.jalz.2010.12.014
发表时间：
2011-07
期刊：
Alzheimer's & dementia : the journal of the Alzheimer's Association
影响因子：
--
作者：
Breitner JC;Baker LD;Montine TJ;Meinert CL;Lyketsos CG;Ashe KH;Brandt J;Craft S;Evans DE;Green RC;Ismail MS;Martin BK;Mullan MJ;Sabbagh M;Tariot PN;ADAPT Research Group
通讯作者：
ADAPT Research Group