Progranulin抑制磷脂酶sPLA2-IIA以控制神经炎症。

Huan Du, Cha Yang, Alissa L Nana, William W Seeley, Marcus Smolka, Fenghua Hu
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摘要

颗粒蛋白(GRN)基因突变导致前颗粒蛋白(PGRN)单倍性不足,是额颞叶变性(FTLD)的主要原因,PGRN多态性与阿尔茨海默病(AD)和帕金森病(PD)有关。PGRN是小胶质细胞介导炎症的关键调节因子,但其机制尚不清楚。在这里,我们报道了PGRN与sPLA2-IIA(一种参与炎症反应的分泌型磷脂酶)相互作用,以下调sPLA2-II a的活性和水平。sPLA2-IIA的表达改变了小鼠的PGRN缺乏表型,并且sPLA2-II A的抑制挽救了PGRN缺乏小鼠的炎症和溶酶体异常。此外,具有GRN突变的FTLD患者在星形胶质细胞中显示sPLA2-IIA水平增加。我们的数据支持sPLA2-IIA作为PGRN的关键靶点和FTLD-GRN的新治疗靶点。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

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WITHDRAWN: Progranulin inhibits phospholipase sPLA2-IIA to control neuroinflammation.

The authors have withdrawn this manuscript because more work is needed to fully define the role of sPLA2-IIA. Therefore, the authors do not wish this work to be cited as reference for the project. If you have any questions, please contact the corresponding author.

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