Microglia as a critical player in both developmental and late-life CNS pathologies.
Microglia as a critical player in both developmental and late-life CNS pathologies.
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小胶质细胞在发育和晚年中枢神经系统病理学中发挥着关键作用。
DOI：
10.1007/s00401-014-1321-z
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发表时间：
2014-09
影响因子：
12.7
通讯作者：
Meyer-Luehmann M
中科院分区：
文献类型：
--
作者：
Derecki NC;Katzmarski N;Kipnis J;Meyer-Luehmann M
小胶质细胞，脑组织中的巨噬细胞，作为从发育到衰老的脑内稳态的关键参与者，正引起越来越多的关注。最近的工作突出了这些曾经神秘的细胞在健康的中枢神经系统功能和长期以来被认为主要是神经元功能障碍的结果的各种病理中的新的和意想不到的作用。在这篇综述中，我们选择关注Rett综合征，其特征是早期神经发育病理学，以及阿尔茨海默病，一种主要与衰老相关的疾病。有趣的是，受体介导的小胶质细胞吞噬作用已经成为发育和晚年大脑病理学的关键功能。在Rett综合征的小鼠模型中，骨髓移植和小胶质细胞样细胞的CNS植入与病理学的惊人改善相关-这些益处被吞噬功能的阻断所消除。在阿尔茨海默氏病中，大规模的全基因组关联研究已被用作鉴定先前未知的易感基因的方法，其突出了小胶质细胞受体作为有希望的治疗调节的新靶点。多光子在体内显微镜提供了一种方法，直接可视化这些靶基因的操纵效果。在这里，我们回顾了最新的发现和概念出现的快速增长的机构的文献例证雷特综合征和迟发性，散发性阿尔茨海默病。
Microglia, the tissue-resident macrophages of the brain, are attracting increasing attention as key players in brain homeostasis from development through aging. Recent works have highlighted new and unexpected roles for these once-enigmatic cells in both healthy central nervous system function and in diverse pathologies long thought to be primarily the result of neuronal malfunction. In this review, we have chosen to focus on Rett syndrome, which features early neurodevelopmental pathology, and Alzheimer’s disease, a disorder associated predominantly with aging. Interestingly, receptor-mediated microglial phagocytosis has emerged as a key function in both developmental and late-life brain pathologies. In a mouse model of Rett syndrome, bone marrow transplant and CNS engraftment of microglia-like cells were associated with surprising improvements in pathology—these benefits were abrogated by block of phagocytic function. In Alzheimer’s disease, large-scale genome-wide association studies have been brought to bear as a method of identifying previously unknown susceptibility genes, which highlight microglial receptors as promising novel targets for therapeutic modulation. Multi-photon in vivo microscopy has provided a method of directly visualizing the effects of manipulation of these target genes. Here, we review the latest findings and concepts emerging from the rapidly growing body of literature exemplified for Rett syndrome and late-onset, sporadic Alzheimer’s disease.
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影响因子：
16.2
作者：
Bhaskar, Kiran;Konerth, Megan;Kokiko-Cochran, Olga N.;Cardona, Astrid;Ransohoff, Richard M.;Lamb, Bruce T.
通讯作者：
Lamb, Bruce T.
影响因子：
25
作者：
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作者：
Coraci, IS;Husemann, J;El Khoury, JB
通讯作者：
El Khoury, JB
影响因子：
82.9
作者：
Backskai, BJ;Kajdasz, ST;Hyman, BT
通讯作者：
Hyman, BT
影响因子：
7.8
作者：
Damani MR;Zhao L;Fontainhas AM;Amaral J;Fariss RN;Wong WT
通讯作者：
Wong WT