MicroRNA-140 silencing represses the incidence of Alzheimer's disease
| Autor: | Hongjiao Wang, Shicun Zhang, Dan Wang, Yang Liu, Chunming Liang, Cihan Di, Yuyuan Mu, Hua Tian |
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| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Male Primary Cell Culture Morris water navigation task PINK1 Biology Hippocampus 03 medical and health sciences 0302 clinical medicine Alzheimer Disease microRNA Autophagy Gene silencing Animals Humans Gene Silencing Maze Learning PI3K/AKT/mTOR pathway Cells Cultured Membrane Potential Mitochondrial Neurons Amyloid beta-Peptides General Neuroscience Peptide Fragments Cell biology Rats Specific Pathogen-Free Organisms Disease Models Animal MicroRNAs 030104 developmental biology Phosphorylation Ectopic expression Reactive Oxygen Species Protein Kinases 030217 neurology & neurosurgery |
| Zdroj: | Neuroscience letters. 758 |
| ISSN: | 1872-7972 |
| Popis: | Alzheimer's disease (AD) is a neurodegenerative condition leading to severe disability from progressive impairments in cognitive functions including memory and learning. Non-coding microRNAs (miRNAs or miRs) have been linked to the pathogenesis of AD. The present study aimed to investigate the clinical significance and biological function of miR-140 in AD. First, we examined the expression of miR-140 and PINK1 in brain tissues of the established AD model rats and neurons cultured with Aβ-derived diffusible ligands (AβDDLs). We identified an interaction between miR-140 and PINK1, and measured spatial learning and memory abilities of the model rats using the Morris water maze (MWM) test. After ectopic expression and depletion experiments in neurons and AD rats, we measured the levels of reactive oxygen species (ROS), and mitochondrial membrane potential (MMP), along with mTOR expression and phosphorylation, and autophagy-related factors. Results showed up-regulation of miR-140 and down-regulation of PINK1 in AD model rats and neurons. PINK1 was verified to be a direct target of miR-140, and silencing of miR-140 suppressed mitochondrial dysfunction, and enhanced autophagy in AD model rats and neurons, as supported by decreased levels of mTOR expression and phosphorylation, β-amyloid p-Tau (Ser396), p-Tau (Thr231), Tau and ROS, and increased MMP levels and expression of Beclin 1 expression and LC3-II/LC3-I. Collectively, functional suppression of miR-140 enhanced autophagy and prevented mitochondrial dysfunction by upregulating PINK1, ultimately suggesting a novel therapeutic target for AD. |
| Databáze: | OpenAIRE |
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