The adhesion and migration of microglia to β-amyloid (Aβ) is decreased with aging and inhibited by Nogo/NgR pathway.
The adhesion and migration of microglia to β-amyloid (Aβ) is decreased with aging and inhibited by Nogo/NgR pathway.
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小胶质细胞对β-淀粉样蛋白（Aβ）的粘附和迁移随着年龄的增长而降低，并受到Nogo/NgR通路的抑制
DOI：
10.1186/s12974-018-1250-1
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发表时间：
2018-07-20
影响因子：
9.3
通讯作者：
Liao H
中科院分区：
文献类型：
--
作者：
Fang Y;Wang J;Yao L;Li C;Wang J;Liu Y;Tao X;Sun H;Liao H
阿尔茨海默病的特点是含有 β-淀粉样蛋白 (Aβ) 的淀粉样斑块逐渐积累，小胶质细胞在 Aβ 的内化和降解中发挥着关键作用。我们之前的研究证实，Nogo-66 与小胶质细胞上表达的 Nogo 受体 (NgR) 结合可抑制体外细胞粘附和迁移。通过粘附测定和transwell测量从不同年龄的WT和APP/PS1小鼠中分离的小胶质细胞的粘附和迁移。在 APP/PS1 转基因小鼠中通过微型渗透泵脑室内注射 NEP1-40（Nogo/NgR 通路的竞争性拮抗剂）2 个月后，测定了小胶质细胞向 Aβ 沉积的募集和 CD36 的表达。在本文中，我们发现衰老导致 WT 和 APP/PS1 小鼠中小胶质细胞粘附和向 fAβ1-42 迁移的减少。小胶质细胞对 fAβ1-42 的粘附和迁移被 NgR 介导的 Nogo 下调，并且在老年小鼠中可以观察到 Nogo 的抑制作用增强。此外，Rho GTPases 通过调节细胞骨架排列，促进了 Nogo 对小胶质细胞粘附和迁移到 fAβ1-42 的影响。此外，阻断 Nogo/NgR 通路可增强 APP/PS1 小鼠中小胶质细胞向 Aβ 沉积的募集和 CD36 的表达。综上所述，Nogo/NgR 通路可以通过调节小胶质细胞粘附和向 Aβ 迁移来参与 AD 中的 Aβ 病理学，并且 Nogo/NgR 通路可能是治疗 AD 的重要靶点。本文的在线版本 (10.1186/s12974-018-1250-1) 包含补充材料，可供授权用户使用。
Alzheimer’s disease is characterized by progressive accumulation of β-amyloid (Aβ)-containing amyloid plaques, and microglia play a critical role in internalization and degradation of Aβ. Our previous research confirmed that Nogo-66 binding to Nogo receptors (NgR) expressed on microglia inhibits cell adhesion and migration in vitro. The adhesion and migration of microglia isolated from WT and APP/PS1 mice from different ages were measured by adhesion assays and transwells. After NEP1-40 (a competitive antagonist of Nogo/NgR pathway) was intracerebroventricularly administered via mini-osmotic pumps for 2 months in APP/PS1 transgenic mice, microglial recruitment toward Aβ deposits and CD36 expression were determined. In this paper, we found that aging led to a reduction of microglia adhesion and migration to fAβ1–42 in WT and APP/PS1 mice. The adhesion and migration of microglia to fAβ1–42 were downregulated by the Nogo, which was mediated by NgR, and the increased inhibitory effects of the Nogo could be observed in aged mice. Moreover, Rho GTPases contributed to the effects of the Nogo on adhesion and migration of microglia to fAβ1–42 by regulating cytoskeleton arrangement. Furthermore, blocking the Nogo/NgR pathway enhanced recruitment of microglia toward Aβ deposits and expression of CD36 in APP/PS1 mice. Taken together, Nogo/NgR pathway could take part in Aβ pathology in AD by modulating microglial adhesion and migration to Aβ and the Nogo/NgR pathway might be an important target for treating AD. The online version of this article (10.1186/s12974-018-1250-1) contains supplementary material, which is available to authorized users.
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