Circular RNA APP contributes to Alzheimer’s disease pathogenesis by modulating microglial polarization via miR-1906/CLIC1 axis

作者：Deng‐Pan Wu, Yan‐Su Wei, Li-Xiang Hou, Yuxuan Du, Qiu‐Qing Yan, Lingling Liu, Yuan‐Dan Zhao, Ruyu Yan, Chao Yu, Zhen-Guo Zhong, Jinlan Huang · 发表于：Alzheimer s Research & Therapy · 年份：2025 · DOI：10.1186/s13195-025-01698-7 · 被引用次数：13 · 研究领域：Circular RNAs in diseases、GDF15 and Related Biomarkers、Alzheimer's disease research and treatments

BACKGROUND: Abnormal microglial polarization phenotypes contribute to the pathogenesis of Alzheimer's disease (AD). Circular RNAs (circRNAs) have garnered increasing attention due to their significant roles in human diseases. Although research has demonstrated differential expression of circRNAs in AD, their specific functions in AD pathogenesis remain largely unexplored. METHODS: CircRNA microarray was performed to identify differentially expressed circRNAs in the hippocampus of APP/PS1 and WT mice. The stability of circAPP was assessed via RNase R treatment assay. CircAPP downstream targets miR-1906 and chloride intracellular channel 1 (CLIC1) were identified using bioinformatics and proteomics, respectively. RT-PCR assay was conducted to detect the expression of circAPP, miR-1906 and CLIC1. Morris water maze (MWM) test, passive avoidance test and novel object recognition task were used to detect cognitive function of APP/PS1 mice. Microglial M1/M2 polarization and AD pathology were assessed using Western blot, flow cytometry and Golgi staining assays. CLIC1 expression and channel activity were evaluated using Western blot and functional chloride channel assays, respectively. The subcellular location of circAPP was assessed via FISH and RT-PCR assays. RNA pull-down assay was performed to detect the interaction of miR-1906 with circAPP and 3' untranslated region (3'UTR) of CLIC1 mRNA. RESULTS: In this study, we identified a novel circRNA, named circAPP, that is encoded by am...