Autophagy is involved in oligodendroglial precursor-mediated clearance of amyloid peptide.
Autophagy is involved in oligodendroglial precursor-mediated clearance of amyloid peptide.
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自噬参与少突胶质前体介导的淀粉样肽清除
DOI：
10.1186/1750-1326-8-27
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发表时间：
2013-08-10
影响因子：
15.1
通讯作者：
Ke ZJ
中科院分区：
文献类型：
--
作者：
Li W;Tang Y;Fan Z;Meng Y;Yang G;Luo J;Ke ZJ
β-淀粉样肽的积聚是阿尔茨海默病（AD）的一个重要标志。人们付出了巨大努力来阐明β-淀粉样肽的降解机制，并制定去除β-淀粉样蛋白积聚的策略。在这项研究中，我们证明少突胶质前体细胞的一个亚群，也称为NG2细胞，是一种新型细胞类型，它能够在AD转基因小鼠以及NG2细胞系中清除β-淀粉样肽。
在APPswe/PS1dE9小鼠（这是一种阿尔茨海默病小鼠模型）中，NG2细胞被募集并聚集在淀粉样斑块周围。在体外，NG2细胞系和原代NG2细胞通过内吞作用机制以时间依赖的方式吞噬β-淀粉样肽。内吞作用分为胞饮作用和吞噬作用。NG2细胞对Aβ42的内化是由肌动蛋白依赖的巨胞饮作用介导的。β-淀粉样肽的存在刺激了NG2细胞中的自噬途径。一旦进入细胞，NG2细胞中的β-淀粉样肽被转运至溶酶体并通过自噬作用降解。
我们的研究结果表明，NG2细胞是一种能够通过内吞作用和自噬作用清除β-淀粉样肽的新型细胞类型。
Accumulation of β-amyloid peptides is an important hallmark of Alzheimer’s disease (AD). Tremendous efforts have been directed to elucidate the mechanisms of β-amyloid peptides degradation and develop strategies to remove β-amyloid accumulation. In this study, we demonstrated that a subpopulation of oligodendroglial precursor cells, also called NG2 cells, were a new cell type that can clear β-amyloid peptides in the AD transgene mice and in NG2 cell line. NG2 cells were recruited and clustered around the amyloid plaque in the APPswe/PS1dE9 mice, which is Alzheimer’s disease mouse model. In vitro, NG2 cell line and primary NG2 cells engulfed β-amyloid peptides through the mechanisms of endocytosis in a time dependent manner. Endocytosis is divided into pinocytosis and phagocytosis. Aβ42 internalization by NG2 cells was mediated by actin-dependent macropinocytosis. The presence of β-amyloid peptides stimulated the autophagic pathway in NG2 cells. Once inside the cells, the β-amyloid peptides in NG2 cells were transported to lysosomes and degraded by autophagy. Our findings suggest that NG2 cells are a new cell type that can clear β-amyloid peptides through endocytosis and autophagy.
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作者：
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