The Role and Therapeutic Potential of Monocytic Cells in Alzheimer's Disease
The Role and Therapeutic Potential of Monocytic Cells in Alzheimer's Disease
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DOI：
10.1002/glia.20973
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发表时间：
2010-06-01
期刊：
影响因子：
6.2
通讯作者：
Koistinaho, Jari
中科院分区：
文献类型：
--
作者：
Malm, Tarja;Koistinaho, Milla;Koistinaho, Jari
阿尔茨海默病（AD）是一种无法治愈的神经退行性痴呆。β-淀粉样蛋白（A β）的异常实质积聚与涉及小胶质细胞和星形胶质细胞的炎症反应有关。大脑中A β和A β沉积水平的增加被认为会导致神经元功能障碍和痴呆症。小胶质细胞是单核细胞来源的脑驻留细胞，具有吞噬A β的潜在能力，但它们也通过增加促炎毒性剂的产生来对A β作出反应。小胶质细胞起源于早期胚胎阶段的成血管细胞中胚层和骨髓（BM）来源的单核细胞，这些单核细胞在整个新生儿发育阶段都是大脑的宿主。最近的研究表明，BM或血液来源的单核细胞被募集到患病的AD脑中，与A β沉积相关，并且与驻留的小胶质细胞相比是A β的更有效的吞噬细胞。这些细胞对A β沉积的清除最近一直在深入研究中，并且可以通过几种不同的机制发生。重要的是，AD患者的外周单核细胞似乎缺乏清除A β的能力。本文将总结血液来源的细胞在AD中的作用的研究结果，并讨论其治疗这种毁灭性疾病的患者的治疗潜力。(C)2010 Wiley-Liss，Inc.
Alzheimer's disease (AD) is a dementing neurodegenerative disorder without a cure. The abnormal parenchymal accumulation of beta-amyloid (A beta) is associated with inflammatory reactions involving microglia and astrocytes. Increased levels of A beta and A beta deposition in the brain are thought to cause neuronal dysfunction and underlie dementia. Microglia, the brain resident cells of monocytic origin, have a potential ability to phagocytose A beta but they also react to A beta by increased production of proinflammatory toxic agents. Microglia originate from hemangioblastic mesoderm during early embryonic stages and from bone marrow (BM)-derived monocytic cells that home the brain throughout the neonatal stage of development. Recent studies indicate that BM or blood-derived monocytes are recruited to the diseased AD brain, associate with the A beta depositions, and are more efficient phagocytes of A beta compared with resident microglia. The clearance of A beta deposition by these cells has been recently under intensive investigation and can occur through several different mechanisms. Importantly, peripheral monocytic cells of patients with AD appear to be deficient in clearing A beta. This review will summarize the findings on the role of blood-derived cells in AD and discuss their therapeutic potential for treating patients suffering from this devastating disease. (C) 2010 Wiley-Liss, Inc.