MicroRNA-132 promotes neurons cell apoptosis and activates Tau phosphorylation by targeting GTDC-1 in Alzheimer's disease
Authors: D-Y Liu
L Zhang
Journal: European review for medical and pharmacological sciences (2019)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: Alzheimer's disease; microRNA; miR-132; neuronal apoptosis; Tau phosphorylation
Affiliations: Department of Pathophysiology, College of Basic Medical Sciences, Chongqing Medical University, Chong-qing, China. .

Abstract:  Objective: Alzheimer's disease (AD) is a neurodegenerative disorder with limited success in the prognosis of patients worldwide. The microRNA (miRNA) technology shows an encouraging trend in the therapeutics of AD. The study aimed to investigate the role of miR-132 and its underlying mechanism involving neuronal apoptosis and Tau phosphorylation in the pathophysiology of AD. Materials and methods: Frozen human postmortem brain samples and neurons cells were used as the specimens. The expression of miR-132 was assessed in AD and mild-cognitive (MCI) group by quantitative Real Time-Polymerase Chain Reaction (qRT-PCR). Then, miR-132 mimic, ASO-miR-132, and corresponding controls were transfected into necrotic cells. Flow cytometry was used to detected cell apoptosis in necrotic cells. qRT-PCR, Western blot, and immunoprecipitation were used to quantify and identify apoptosis-related factors (Bax and Bcl-2), Tau phosphorylation, CDK-5, GTDC-1 levels in necrotic cells. Furthermore, Dual-Luciferase reporter assay was used to predict a direct target of miR-132. Results: The expression of miR-132 was significantly higher in patients with MCI and AD compared to the normal group. Overexpression of miR-132 induced neuronal apoptosis by increasing Bax and decreasing Bcl-2 and also up-regulated phosphorylation of Tau, Rb, Histone H1, and CDK-5 expressions. Besides, GTDC-1 was identified as a direct target gene of miR-132. However, GTDC-1 markedly reversed the promoting effect of miR-132 on cell apoptosis and Tau phosphorylation. Conclusions: MiR-132 plays an important role in the pathogenesis of AD via regulation of cell apoptosis and GTDC-1/CDK-5/Tau phosphorylation signaling mechanism. It may be a potential therapeutic target in patients with AD. 

Retracted: No

PubPeer comments:
 The Western blots and other figures in this paper have an interesting layout that appears to be shared with many other papers, as discussed in a January 2020 post on Leonid Schneider s blog: https: forbetterscience.com 2020 01 24 the-full-service-paper-mill-and-its-chinese-customers The list of these papers is available here: https: docs.google.com spreadsheets d 1KXqTAyl4j-jVorFPMD2XRpr76LcIKJ0CVyIvRj0exYQ edit?usp=sharing In almost all papers, Western blot panels within the same figure, and across figures and papers, appear to share the same background, while the bands are regularly spaced, all have similar rounded edges without the usual smudges and specks, and with some bands showing a recognizable  jumping sardine shape. Many papers have  cell viability and  apoptotic cells graphs. To illustrate the recognizable layout of the blots in this paper, here is Figure 3.  In some of these papers, including this one, flow cytometry plots show an unnaturally dense and well defined  hairball of events in Q3 with a few regularly spaced events in Q1 and Q2, and a rectangular or crab-shaped block of events in Q4. To illustrate the unexpected features of the flow cytometry plots, here is Figure 2.  ,