miR-132 loss de-represses ITPKB and aggravates amyloid and TAU pathology in Alzheimer's brain.
miR-132 loss de-represses ITPKB and aggravates amyloid and TAU pathology in Alzheimer's brain.
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DOI：
10.15252/emmm.201606520
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发表时间：
2016-09
影响因子：
11.1
通讯作者：
De Strooper B
中科院分区：
文献类型：
--
作者：
Salta E;Sierksma A;Vanden Eynden E;De Strooper B
microRNA-132（miR-132）参与神经系统中的促生存、抗炎和记忆促进功能，并在阿尔茨海默病（AD）中持续下调。然而，miR-132缺陷是否以及如何影响AD病理学仍然没有得到解决。我们在此显示，在AD小鼠模型中，miR-132缺失通过肌醇1，4，5-三磷酸3-激酶B（ITPK B）上调加重淀粉样蛋白和TAU病理。这导致ERK 1/2和BACE 1活性增加和TAU磷酸化升高。我们证实了在三个不同的人类AD患者队列中miR-132的下调和ITPKB的上调，表明该途径在AD中的病理相关性。
microRNA‐132 (miR‐132) is involved in prosurvival, anti‐inflammatory and memory‐promoting functions in the nervous system and has been found consistently downregulated in Alzheimer's disease (AD). Whether and how miR‐132 deficiency impacts AD pathology remains, however, unaddressed. We show here that miR‐132 loss exacerbates both amyloid and TAU pathology via inositol 1,4,5‐trisphosphate 3‐kinase B (ITPKB) upregulation in an AD mouse model. This leads to increased ERK1/2 and BACE1 activity and elevated TAU phosphorylation. We confirm downregulation of miR‐132 and upregulation of ITPKB in three distinct human AD patient cohorts, indicating the pathological relevance of this pathway in AD.