Phagocytic clearance in neurodegeneration.
Phagocytic clearance in neurodegeneration.
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DOI：
10.1016/j.ajpath.2010.12.051
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发表时间：
2011-04
期刊：
影响因子：
--
通讯作者：
J. Sokolowski;J. Mandell
中科院分区：
文献类型：
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作者：
J. Sokolowski;J. Mandell
在无脊椎动物模式生物和哺乳动物免疫系统中，吞噬细胞清除凋亡细胞和碎片的细胞和分子机制已经得到了深入的研究。这一进化上保守的过程有多种目的。死亡细胞的未清除碎片或聚集的蛋白质可能是有毒的，并可能引发夸大的炎症反应。尽管凋亡性细胞死亡和碎片堆积是神经退行性疾病的主要特征，但对中枢神经系统(CNS)这一重要的体内平衡功能的关注相对较少。这篇综述试图总结我们对中枢神经系统吞噬细胞清除的知识，重点是视网膜变性，其形式是由已知吞噬细胞途径中的基因突变引起的，以及阿尔茨海默病(AD)。免疫可以促进淀粉样蛋白-β的吞噬清除，这一发现激发了人们对AD吞噬清除机制的兴趣；然而，对AD和其他神经退行性疾病中神经元和突触身体的清除知之甚少。由于吞噬活性的调节与细胞因子信号转导交织在一起，本文还讨论了中枢神经系统炎症、神经胶质反应和吞噬清除之间的关系。
The cellular and molecular mechanisms of phagocytic clearance of apoptotic cells and debris have been intensely studied in invertebrate model organisms and in the mammalian immune system. This evolutionarily conserved process serves multiple purposes. Uncleared debris from dying cells or aggregated proteins can be toxic and may trigger exaggerated inflammatory responses. Even though apoptotic cell death and debris accumulation are key features of neurodegenerative diseases, relatively little attention has been paid to this important homeostatic function in the central nervous system (CNS). This review attempts to summarize our knowledge of phagocytic clearance in the CNS, with a focus on retinal degeneration, forms of which are caused by mutations in genes within known phagocytic pathways, and on Alzheimer's disease (AD). Interest in phagocytic clearance mechanisms in AD was stimulated by the discovery that immunization could promote phagocytic clearance of amyloid-β; however, much less is known about clearance of neuronal and synaptic corpses in AD and other neurodegenerative diseases. Because the regulation of phagocytic activity is intertwined with cytokine signaling, this review also addresses the relationships among CNS inflammation, glial responses, and phagocytic clearance.