Involvement of Astrocytes in Alzheimer's Disease from a Neuroinflammatory and Oxidative Stress Perspective.
Involvement of Astrocytes in Alzheimer's Disease from a Neuroinflammatory and Oxidative Stress Perspective.
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DOI：
10.3389/fnmol.2017.00427
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发表时间：
2017
影响因子：
4.8
通讯作者：
Mora-Muñoz L
中科院分区：
文献类型：
--
作者：
González-Reyes RE;Nava-Mesa MO;Vargas-Sánchez K;Ariza-Salamanca D;Mora-Muñoz L
阿尔茨海默病（AD）是人类一种常见且具有破坏性的神经退行性疾病，但目前尚未开发出治愈方法。尽管已经提出了许多解释性理论，但确切的病理生理机制尚不清楚。由于星形胶质细胞在大脑稳态中的重要性，它们已成为 AD 研究的有趣目标。在 AD 患者的大脑以及 AD 体外和体内动物模型中观察到星形胶质细胞功能的变化。 β 淀粉样蛋白 (Aβ) 的存在已被证明会破坏胶质细胞传递、神经递质摄取并改变星形胶质细胞中的钙信号传导。此外，星形胶质细胞表达载脂蛋白E并参与Aβ的产生、降解和去除。此外，星形胶质细胞的变化先于 AD 中观察到的其他病理特征，表明星形胶质细胞在这种疾病中发挥了早期作用。星形胶质细胞参与中枢神经系统的炎症/免疫反应。 Aβ的存在激活不同的细胞受体和细胞内信号通路，主要是晚期糖基化终末产物受体/活化B细胞核因子κ轻链增强子(NF-κB)通路，负责星形胶质细胞中促炎细胞因子和趋化因子的转录。这些促炎剂的释放可能会引起细胞损伤，甚至刺激星形胶质细胞中 Aβ 的产生。此外，Aβ 还会诱导星形胶质细胞出现氧化应激 (OS) 以及活性氧和活性氮的产生，从而影响细胞内钙水平、NADPH 氧化酶 (NOX)、NF-κB 信号传导、谷氨酸摄取（增加兴奋性毒性风险）和线粒体功能。在 AD 中观察到过度的神经炎症和 OS，星形胶质细胞似乎与这两者有关。星形胶质细胞中的 Aβ/NF-κB 相互作用可能在 AD 中的这些炎症和 OS 变化中发挥核心作用。在本文中，我们还讨论了治疗措施，强调了星形胶质细胞在 AD 病理学中的重要性。在星形胶质细胞中探索了几种涉及酚类（姜黄素）、植物雌激素（金雀异黄素）、神经甾类和其他天然植物化学物质的新治疗方法，在改善认知和减轻神经炎症方面获得了一些有希望的结果。还提出了包含星形胶质细胞并旨在减少 AD 中 OS 的新策略。这些药物包括雌激素受体激动剂（天竺葵素）、Bambusae concretio Salicea、红曲霉素和各种抗氧化剂，如白藜芦醇、生育三烯酚、花青素和表儿茶素，在 AD 模型中显示出有益的作用。
Alzheimer disease (AD) is a frequent and devastating neurodegenerative disease in humans, but still no curative treatment has been developed. Although many explicative theories have been proposed, precise pathophysiological mechanisms are unknown. Due to the importance of astrocytes in brain homeostasis they have become interesting targets for the study of AD. Changes in astrocyte function have been observed in brains from individuals with AD, as well as in AD in vitro and in vivo animal models. The presence of amyloid beta (Aβ) has been shown to disrupt gliotransmission, neurotransmitter uptake, and alter calcium signaling in astrocytes. Furthermore, astrocytes express apolipoprotein E and are involved in the production, degradation and removal of Aβ. As well, changes in astrocytes that precede other pathological characteristics observed in AD, point to an early contribution of astroglia in this disease. Astrocytes participate in the inflammatory/immune responses of the central nervous system. The presence of Aβ activates different cell receptors and intracellular signaling pathways, mainly the advanced glycation end products receptor/nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) pathway, responsible for the transcription of pro-inflammatory cytokines and chemokines in astrocytes. The release of these pro-inflammatory agents may induce cellular damage or even stimulate the production of Aβ in astrocytes. Additionally, Aβ induces the appearance of oxidative stress (OS) and production of reactive oxygen species and reactive nitrogen species in astrocytes, affecting among others, intracellular calcium levels, NADPH oxidase (NOX), NF-κB signaling, glutamate uptake (increasing the risk of excitotoxicity) and mitochondrial function. Excessive neuroinflammation and OS are observed in AD, and astrocytes seem to be involved in both. The Aβ/NF-κB interaction in astrocytes may play a central role in these inflammatory and OS changes present in AD. In this paper, we also discuss therapeutic measures highlighting the importance of astrocytes in AD pathology. Several new therapeutic approaches involving phenols (curcumin), phytoestrogens (genistein), neuroesteroids and other natural phytochemicals have been explored in astrocytes, obtaining some promising results regarding cognitive improvements and attenuation of neuroinflammation. Novel strategies comprising astrocytes and aimed to reduce OS in AD have also been proposed. These include estrogen receptor agonists (pelargonidin), Bambusae concretio Salicea, Monascin, and various antioxidatives such as resveratrol, tocotrienol, anthocyanins, and epicatechin, showing beneficial effects in AD models.
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DOI：
10.1523/jneurosci.1064-09.2009
发表时间：
2009-10-14
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Abdul HM;Sama MA;Furman JL;Mathis DM;Beckett TL;Weidner AM;Patel ES;Baig I;Murphy MP;LeVine H 3rd;Kraner SD;Norris CM
通讯作者：
Norris CM
DOI：
10.1016/s0169-328x(98)00066-7
发表时间：
1998-06-01
期刊：
MOLECULAR BRAIN RESEARCH
影响因子：
--
作者：
Bales, KR;Du, YS;Paul, SM
通讯作者：
Paul, SM
影响因子：
5.3
作者：
Abramov, AY;Canevari, L;Duchen, MR
通讯作者：
Duchen, MR
影响因子：
3.4
作者：
Araque, A;Parpura, V;Haydon, PG
通讯作者：
Haydon, PG
影响因子：
3.3
作者：
Askarova, S.;Yang, X.;Sheng, W.;Sun, G. Y.;Lee, J. C-M
通讯作者：
Lee, J. C-M