Abstract
Alzheimer’s disease (AD) is a common dementia and a heterogeneous disease. Previous research has validated that microRNAs (miRNAs) are pivotal regulators in the initiation and development of tremendous diseases including AD. MicroRNA-485-5p (miR-485-5p) was reported to be an important participant implicated in several neurological diseases, but its role in AD still needs to be further investigated. In this research, we explored the biological function of miR-485-5p in AD. RT-qPCR revealed that miR-485-5p expression was downregulated in the hippocampus of APP/PS1 mice. Additionally, miR-485-5p overexpression facilitated the learning and memory capabilities of APP/PS1 mice according to Morris water maze test, fear conditioning test, and immunofluorescent staining. Moreover, CCK-8 assay, flow cytometric analysis, and western blot analysis suggested that miR-485-5p overexpression promoted pericyte viability and prohibited pericyte apoptosis in APP/PS1 mice. Mechanistically, miR-485-5p directly targeted PACS1 in pericytes, as shown in a luciferase reporter assay. In rescue assays, PACS1 overexpression countervailed the effect of miR-485-5p overexpression on pericyte viability and apoptosis. In conclusion, miR-485-5p ameliorates AD progression by targeting PACS1.
Highlights
Alzheimer’s disease (AD) is a common dementia and a heterogeneous disease
Though there are no effective treatments for the cure of AD [29,30], the prevention of pericyte apoptosis has been proposed to be efficient in alleviating AD progression [4,31,32]
We investigated the effect of miR-485-5p on pericyte apoptosis since miR485-5p has been confirmed to regulate neuron survival [35]
Summary
Abstract: Alzheimer’s disease (AD) is a common dementia and a heterogeneous disease. Previous research has validated that microRNAs (miRNAs) are pivotal regulators in the initiation and development of tremendous diseases including AD. MicroRNA-485-5p (miR-485-5p) was reported to be an important participant implicated in several neurological diseases, but its role in AD still needs to be further investigated. Previous research demonstrated that the damage of pericytes may lead to blood-brain barrier (BBB) breakdown, one of the early signs of neurodegenerative diseases including AD [7,8]. The progressive degeneration of pericytes can boost Alzheimerlike neurodegeneration in transgenic APP/PS1 mice according to previous studies, highlighting that prohibiting pericyte apoptosis might be beneficial to prevent or slow down the development of AD [9,10]. We established a murine AD model to investigate the learning and memory abilities of APP/PS1 mice and the viability and apoptosis of pericyte in this study. We explored the function and mechanism of miR-485-5p and its target gene PACS1 in the progression of AD.
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