Uptake, degradation, and release of fibrillar and soluble forms of Alzheimer's amyloid β-peptide by microglial cells
Uptake, degradation, and release of fibrillar and soluble forms of Alzheimer's amyloid β-peptide by microglial cells
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DOI：
10.1074/jbc.274.45.32301
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发表时间：
1999-11-05
影响因子：
4.8
通讯作者：
Maxfield, FR
中科院分区：
文献类型：
--
作者：
Chung, HY;Brazil, MI;Maxfield, FR
小胶质细胞是一种吞噬细胞，是中枢神经系统的主要炎症反应细胞。在阿尔茨海默病患者的大脑中，活化的小胶质细胞集中在含有39-43氨基酸A β肽的致密淀粉样蛋白沉积物区域。我们检测了小胶质细胞对纤维状A β (fA β)或可溶性A β (sA β)的吸收、降解和释放。我们发现，尽管在3天内观察到fA β的一些降解，但在接下来的9天内没有观察到进一步的降解，相反，有一个缓慢释放完整的A β。较差的降解不是由于溶酶体功能的抑制，因为α 2巨球蛋白的降解率不受后期内体/溶酶体中fA β的存在的影响。与fA β相反，sA β的内化是不饱和的。内化后，sA β从小胶质细胞迅速释放，很少被降解。这些数据表明fA β和sA β与小胶质细胞的相互作用不同，但在内化后，两者的很大一部分被释放而不降解。
Microglia are phagocytic cells that are the main inflammatory response cells of the central nervous system, In Alzheimer's disease brain, activated microglia are concentrated in regions of compact amyloid deposits that contain the 39-43-amino acid A beta peptide. We examined the uptake, degradation, and release of small aggregates of fibrillar A beta (fA beta) or soluble A beta (sA beta) by microglia, We found that although some degradation of fA beta was observed over 3 days, no further degradation was observed over the next 9 days, Instead, there was a slow release of intact A beta. The poor degradation was not due to inhibition of lysosomal function, since the rate of alpha 2-macroglobulin degradation was not affected by the presence of fA beta in the late endosomes/lysosomes. In contrast to fA beta, internalization of sA beta was not saturable. After internalization, sA beta was released rapidly from microglia, and very little was degraded. These data show that fA beta and sA beta interact differently with microglia but that after internalization a large fraction of both are released without degradation.