{"title":"miR-29c-3p 通过调节 beta 位点淀粉样前体蛋白切割酶 1 减轻阿尔茨海默病中 beta 淀粉样蛋白诱导的神经毒性","authors":"X Wang, M Li, Y Hu","doi":"","DOIUrl":null,"url":null,"abstract":"<p><p>The aberrantly expressed microRNAs (miRNAs) including miR-29c-3p have been reported in the brains of Alzheimer's disease (AD) patients in recent researches. Nevertheless, the functional role and underlying molecular mechanism of miR-29c-3p in AD pathogenesis are still not well elucidated. The purpose of this study was to examine whether miR-29c-3p regulated beta-Ameyloid (Abeta)-induced neurotoxicity by targeting beta-site amyloid precursor protein-cleaving enzyme 1 (BACE1). The expressions of miR 29c 3p and BACE1 mRNA and protein levels in Abeta-treated PC12 cellular AD model were examined by qRT-PCR and western blot analyses. Luciferase reporter assay verified the potential target of miR 29c 3p. Cell viability, apoptosis, and caspase-3 activity in PC12 cells were detected by the MTT assay, flow cytometry, and caspase-3 activity assay, respectively. Our results indicated that miR-29c-3p downregulation and BACE1 upregulation existed in the cellular AD model of PC12 cells. Moreover, miR-29c-3p directly inhibited BACE1 expression. miR-29c-3p overexpression and BACE1 knockdown strengthened Abeta-induced cell apoptosis, and caspase-3 activity in PC12 cells, which was partially eliminated by over-expression of BACE1. Conversely, BACE1 knockdown reversed the miR-29c-3p inhibition- mediated inhibitory effect on Abeta-induced cell toxicity, apoptosis, and caspase-3 activity in PC12 cells. Considering, miR-29c-3p attenuated Abeta-induced neurotoxicity through targeting BACE1 in an cellular AD model of PC12, providing a potential therapeutic target for AD treatment.</p>","PeriodicalId":20235,"journal":{"name":"Physiological research","volume":null,"pages":null},"PeriodicalIF":1.9000,"publicationDate":"2023-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10805262/pdf/","citationCount":"0","resultStr":"{\"title\":\"miR-29c-3p Attenuates beta-Amyloid-Induced Neurotoxicity in Alzheimer's Disease Through Regulating beta-Site Amyloid Precursor Protein-Cleaving Enzyme 1.\",\"authors\":\"X Wang, M Li, Y Hu\",\"doi\":\"\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>The aberrantly expressed microRNAs (miRNAs) including miR-29c-3p have been reported in the brains of Alzheimer's disease (AD) patients in recent researches. Nevertheless, the functional role and underlying molecular mechanism of miR-29c-3p in AD pathogenesis are still not well elucidated. The purpose of this study was to examine whether miR-29c-3p regulated beta-Ameyloid (Abeta)-induced neurotoxicity by targeting beta-site amyloid precursor protein-cleaving enzyme 1 (BACE1). The expressions of miR 29c 3p and BACE1 mRNA and protein levels in Abeta-treated PC12 cellular AD model were examined by qRT-PCR and western blot analyses. Luciferase reporter assay verified the potential target of miR 29c 3p. Cell viability, apoptosis, and caspase-3 activity in PC12 cells were detected by the MTT assay, flow cytometry, and caspase-3 activity assay, respectively. Our results indicated that miR-29c-3p downregulation and BACE1 upregulation existed in the cellular AD model of PC12 cells. Moreover, miR-29c-3p directly inhibited BACE1 expression. miR-29c-3p overexpression and BACE1 knockdown strengthened Abeta-induced cell apoptosis, and caspase-3 activity in PC12 cells, which was partially eliminated by over-expression of BACE1. Conversely, BACE1 knockdown reversed the miR-29c-3p inhibition- mediated inhibitory effect on Abeta-induced cell toxicity, apoptosis, and caspase-3 activity in PC12 cells. Considering, miR-29c-3p attenuated Abeta-induced neurotoxicity through targeting BACE1 in an cellular AD model of PC12, providing a potential therapeutic target for AD treatment.</p>\",\"PeriodicalId\":20235,\"journal\":{\"name\":\"Physiological research\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":1.9000,\"publicationDate\":\"2023-12-31\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10805262/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Physiological research\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q3\",\"JCRName\":\"PHYSIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Physiological research","FirstCategoryId":"3","ListUrlMain":"","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"PHYSIOLOGY","Score":null,"Total":0}
引用次数: 0
摘要
最近的研究发现,阿尔茨海默病(AD)患者大脑中存在异常表达的微RNA(miRNA),其中包括miR-29c-3p。然而,miR-29c-3p 在阿尔茨海默病(AD)发病机制中的功能作用和潜在分子机制仍未得到很好的阐明。本研究旨在探讨miR-29c-3p是否通过靶向β位淀粉样前体蛋白切割酶1(BACE1)来调控β位淀粉样蛋白(ABETA)诱导的神经毒性。qRT-PCR 和 Western 印迹分析检测了经 Abeta 处理的 PC12 细胞 AD 模型中 miR 29c 3p 和 BACE1 mRNA 及蛋白水平的表达。荧光素酶报告实验验证了 miR 29c 3p 的潜在靶点。MTT 试验、流式细胞术和 caspase-3 活性测定分别检测了 PC12 细胞的活力、凋亡和 caspase-3 活性。结果表明,在细胞AD模型中,PC12细胞存在miR-29c-3p下调和BACE1上调。此外,miR-29c-3p 直接抑制 BACE1 的表达。miR-29c-3p 的过表达和 BACE1 的敲除加强了阿贝塔诱导的细胞凋亡和 PC12 细胞中的 caspase-3 活性,而 BACE1 的过表达则部分消除了这一作用。相反,BACE1 的敲除逆转了 miR-29c-3p 抑制介导的对阿贝塔诱导的 PC12 细胞毒性、细胞凋亡和 caspase-3 活性的抑制作用。综上所述,miR-29c-3p 在细胞 AD 模型 PC12 中通过靶向 BACE1 减轻了阿贝塔诱导的神经毒性,为治疗 AD 提供了一个潜在的治疗靶点。
miR-29c-3p Attenuates beta-Amyloid-Induced Neurotoxicity in Alzheimer's Disease Through Regulating beta-Site Amyloid Precursor Protein-Cleaving Enzyme 1.
The aberrantly expressed microRNAs (miRNAs) including miR-29c-3p have been reported in the brains of Alzheimer's disease (AD) patients in recent researches. Nevertheless, the functional role and underlying molecular mechanism of miR-29c-3p in AD pathogenesis are still not well elucidated. The purpose of this study was to examine whether miR-29c-3p regulated beta-Ameyloid (Abeta)-induced neurotoxicity by targeting beta-site amyloid precursor protein-cleaving enzyme 1 (BACE1). The expressions of miR 29c 3p and BACE1 mRNA and protein levels in Abeta-treated PC12 cellular AD model were examined by qRT-PCR and western blot analyses. Luciferase reporter assay verified the potential target of miR 29c 3p. Cell viability, apoptosis, and caspase-3 activity in PC12 cells were detected by the MTT assay, flow cytometry, and caspase-3 activity assay, respectively. Our results indicated that miR-29c-3p downregulation and BACE1 upregulation existed in the cellular AD model of PC12 cells. Moreover, miR-29c-3p directly inhibited BACE1 expression. miR-29c-3p overexpression and BACE1 knockdown strengthened Abeta-induced cell apoptosis, and caspase-3 activity in PC12 cells, which was partially eliminated by over-expression of BACE1. Conversely, BACE1 knockdown reversed the miR-29c-3p inhibition- mediated inhibitory effect on Abeta-induced cell toxicity, apoptosis, and caspase-3 activity in PC12 cells. Considering, miR-29c-3p attenuated Abeta-induced neurotoxicity through targeting BACE1 in an cellular AD model of PC12, providing a potential therapeutic target for AD treatment.
期刊介绍:
Physiological Research is a peer reviewed Open Access journal that publishes articles on normal and pathological physiology, biochemistry, biophysics, and pharmacology.
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