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- Title
miR-143-3p Inhibits Aberrant Tau Phosphorylation and Amyloidogenic Processing of APP by Directly Targeting DAPK1 in Alzheimer's Disease.
- Authors
Wang, Long; Shui, Xindong; Mei, Yingxue; Xia, Yongfang; Lan, Guihua; Hu, Li; Zhang, Mi; Gan, Chen-Ling; Li, Ruomeng; Tian, Yuan; Wang, Quling; Gu, Xi; Chen, Dongmei; Zhang, Tao; Lee, Tae Ho
- Abstract
The neuropathology of Alzheimer's disease (AD) is characterized by intracellular aggregation of hyperphosphorylated tau and extracellular accumulation of beta-amyloid (Aβ). Death-associated protein kinase 1 (DAPK1), as a novel therapeutic target, shows promise for the treatment of human AD, but the regulatory mechanisms of DAPK1 expression in AD remain unclear. In this study, we identified miR-143-3p as a promising candidate for targeting DAPK1. miR-143-3p directly bound to the 3′ untranslated region of human DAPK1 mRNA and inhibited its translation. miR-143-3p decreased tau phosphorylation and promoted neurite outgrowth and microtubule assembly. Moreover, miR-143-3p attenuated amyloid precursor protein (APP) phosphorylation and reduced the generation of Aβ40 and Aβ42. Furthermore, restoring DAPK1 expression with miR-143-3p antagonized the effects of miR-143-3p in attenuating tau hyperphosphorylation and Aβ production. In addition, the miR-143-3p levels were downregulated and correlated inversely with the expression of DAPK1 in the hippocampus of AD patients. Our results suggest that miR-143-3p might play critical roles in regulating both aberrant tau phosphorylation and amyloidogenic processing of APP by targeting DAPK1 and thus offer a potential novel therapeutic strategy for AD.
- Subjects
MICRORNA; ALZHEIMER'S disease; PHOSPHORYLATION; AMYLOID beta-protein precursor; TAU proteins; PROTEIN kinases
- Publication
International Journal of Molecular Sciences, 2022, Vol 23, Issue 14, p7992
- ISSN
1661-6596
- Publication type
Article
- DOI
10.3390/ijms23147992