Engulfment of Toxic Amyloid β-protein in Neurons and Astrocytes Mediated by MEGF10
Engulfment of Toxic Amyloid β-protein in Neurons and Astrocytes Mediated by MEGF10
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DOI：
10.1016/j.neuroscience.2020.07.016
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发表时间：
2020-09-01
期刊：
影响因子：
3.3
通讯作者：
Komano, Hiroto
中科院分区：
文献类型：
--
作者：
Fujita, Yu;Maeda, Tomoji;Komano, Hiroto
淀粉样β蛋白(Aβ)包括Aβ42和Aβ43，是阿尔茨海默病(AD)的致病因子。大脑中不需要的物质，包括Aβ，通常通过吞噬受体被小胶质细胞、星形胶质细胞或神经元清除。我们观察到神经元和星形胶质细胞吞噬了Aβ42和Aβ43，它们的神经毒性比Aβ40更强。我们先前发现多个EGF样域10(MEGF10)在消除细胞凋亡中起重要作用，并且在哺乳动物神经元和星形胶质细胞中表达。因此，我们评估了MEGF10是否参与了表达MEGF10的神经元和星形胶质细胞中Aβ42和Aβ43的吞噬。我们发现，表达MEGF10的星形胶质细胞和神经元吞噬了Aβ42和Aβ43，但不吞噬Aβ40。此外，神经元和星形胶质细胞与Aβ42和Aβ43A孵育可促进MEGF10的磷酸化，而与Aβ40孵育则没有这种增强作用。我们的研究结果表明，在神经元和星形胶质细胞中，MEGF10具有吞噬Aβ42和Aβ43的受体功能。(C)2020 IBRO。爱思唯尔有限公司出版。保留所有权利。
Amyloid-beta proteins (A beta), including A beta 42 and A beta 43, are known pathogenesis factors of Alzheimer's disease (AD). Unwanted substances in the brain, including A beta, are generally removed by microglia, astrocytes, or neurons via a phagocytosis receptor. We observed that neurons and astrocytes engulfed A beta 42 and A beta 43, which are more neurotoxic than A beta 40. We previously showed that multiple-EGF like domains 10 (MEGF10) plays an important role in apoptotic cell elimination and is expressed in mammalian neurons and astrocytes. Therefore, we assessed whether MEGF10 is involved in A beta 42 and A beta 43 engulfment in MEGF10-expressing neurons and astrocytes. We found that MEGF10-expressing astrocytes and neurons engulfed A beta 42 and A beta 43 but not A beta 40. Furthermore, incubation of the neurons and astrocytes with A beta 42 and A beta 43a ugmented MEGF10 phosphorylation; however, incubation with A beta 40 did not have this augmenting effect. Our findings suggest that MEGF10 plays a phagocytosis receptor function for A beta 42 and A beta 43 in neurons and astrocytes. (C) 2020 IBRO. Published by Elsevier Ltd. All rights reserved.