Microglia and inflammation in Alzheimer's disease.
Microglia and inflammation in Alzheimer's disease.
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DOI：
10.2174/187152710791012071
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发表时间：
2010-04
期刊：
影响因子：
--
通讯作者：
Landreth GE
中科院分区：
文献类型：
--
作者：
Mandrekar-Colucci S;Landreth GE
自魏尔啸首次发现小胶质细胞以来，150年已经过去了。虽然这种细胞类型已经得到了很好的研究，但小胶质细胞在许多中枢神经系统疾病的病理学中的作用仍然是个谜。人们普遍认为，小胶质细胞介导的炎症有助于阿尔茨海默病（AD）的进展;然而，这些细胞有助于AD相关炎症的确切机制仍有待阐明。在AD脑中，发现小胶质细胞与淀粉样蛋白β（Aβ）沉积密切相关。AD脑的组织学检查以及细胞培养研究表明，小胶质细胞与纤维状Aβ的相互作用导致其表型活化。这些细胞转化为经典的“活化”表型导致产生对CNS有害的趋化因子、神经毒性细胞因子和活性氧和氮物质。然而，小胶质细胞也通过其吞噬Aβ颗粒和清除可溶性Aβ的能力发挥神经保护作用。这些细胞已被证明在组织修复和炎症中发挥不可或缺的作用，近年来人们已经认识到，这种细胞类型能够通过改变其激活状态来促进对病原体的更复杂的反应。各种新的发现表明，它们在中枢神经系统中的作用比以前认识到的要复杂得多。在这篇综述中，我们讨论了小胶质细胞在正常大脑中的作用及其表型异质性，以及这可能在AD相关的病理生理学中发挥的作用。我们触及了关于它们识别和清除Aβ肽的能力以及更具争议性的主题，包括小胶质细胞的各种激活状态和外周巨噬细胞或单核细胞浸润大脑的能力。
One hundred and fifty years have elapsed since the original discovery of the microglial cell by Virchow. While this cell type has been well studied, the role of microglia in the pathology of many central nervous system diseases still remains enigmatic. It is widely accepted that microglial-mediated inflammation contributes to the progression of Alzheimer’s disease (AD); however, the precise mechanisms through which these cells contribute to AD-related inflammation remains to be elucidated. In the AD brain, microglial cells are found in close association with amyloid β (Aβ) deposits. Histological examination of AD brains as well as cell culture studies have shown that the interaction of microglia with fibrillar Aβ leads to their phenotypic activation. The conversion of these cells into a classically ‘activated’ phenotype results in production of chemokines, neurotoxic cytokines and reactive oxygen and nitrogen species that are deleterious to the CNS. However, microglia also exert a neuroprotective role through their ability to phagocytose Aβ particles and clear soluble forms of Aβ. These cells have been documented to play integral roles in tissue repair and inflammation, and in recent years it has been appreciated that this cell type is capable of facilitating a more complex response to pathogens by changing their activation status. A variety of new findings indicate that their role in the central nervous system is far more complex than previously appreciated. In this review we discuss the role of microglia in the normal brain and their phenotypic heterogeneity and how this may play a role in AD-related pathophysiology. We touch on what is known about their ability to recognize and clear Aβ peptides as well as more controversial topics, including various activation states of microglia and the ability of peripheral macrophages or monocytes to infiltrate the brain.
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影响因子：
2.5
作者：
Bulloch, Karen;Miller, Melinda M.;McEwen, Bruce S.
通讯作者：
McEwen, Bruce S.
影响因子：
168.9
作者：
Cagnin, A;Brooks, DJ;Banati, RB
通讯作者：
Banati, RB
影响因子：
9.3
作者：
Colton CA;Mott RT;Sharpe H;Xu Q;Van Nostrand WE;Vitek MP
通讯作者：
Vitek MP
影响因子：
4.8
作者：
Chung, HY;Brazil, MI;Maxfield, FR
通讯作者：
Maxfield, FR
影响因子：
3.4
作者：
Calvo, CF;Yoshimura, T;Mallat, M
通讯作者：
Mallat, M