MiR-191-5p Attenuates Tau Phosphorylation, Aβ Generation, and Neuronal Cell Death by Regulating Death-Associated Protein Kinase 1

• DOI: 10.1021/acschemneuro.2c00423
• Publication Date: 2022-12-01T15:30:47Z
• Authors: Long Wang; Xindong Shui; Mi Zhang; Yingxue Mei; Yongfang Xia; Guihua Lan; Li Hu; Chen-Ling Gan; Yuan Tian; Ruomeng Li; Xi Gu; Tao Zhang; Dongmei Chen; Tae Ho Lee
• Keywords: Neurite; Tau protein

Dysregulation of microRNAs has been implicated in diverse diseases, including Alzheimer's disease (AD). MiR-191-5p plasma/serum identified as a novel and promising noninvasive diagnostic biomarker for AD. However, whether miR-191-5p is involved AD pathogenesis largely unknown, its levels human brains are undetermined. Herein, we demonstrated that downregulated tau phosphorylation at multiple AD-related sites promoted neurite outgrowth using immunoblotting, immunofluorescence, assays. Moreover, immunoblotting enzyme-linked immunosorbent assays indicated decreased amyloid precursor protein beta-amyloid (Aβ) generation. Furthermore, reduced ceramide-induced neuronal cell death analyzed by trypan blue staining, the situ detection kit, Annexin V-FITC/PI flow cytometry. Next, verified death-associated kinase 1 (DAPK1) was direct target through dual luciferase reporter assay confirmed effects were antagonized restoration DAPK1 expression. Finally, hippocampal level found to be humans with compared controls inversely correlated expression level. Collectively, these findings suggest might exert inhibitory on phosphorylation, Aβ secretion, directly targeting DAPK1, providing an attractive therapeutic option