MicroRNA-137-5p靶向USP30改善阿尔茨海默病  

MicroRNA-137-5p improves the condition of Alzheimer’s disease by targeting USP30

作　　者：姜扬[1] 卞威[2] 刘婷[3] 隋轶[1] 任莉[1] 曹晓攀 肖莹[1] 徐冰 JIANG Yang;BIAN Wei;LIU Ting(Department of Neurology,the First People’s Hospital of Shenyang,Liaoning,Shenyang 110041,China;不详)

机构地区：[1]辽宁省沈阳市第一人民医院神经内科,110041 [2]辽宁省沈阳市第一人民医院神经外科,110041 [3]辽宁省沈阳市肛肠医院 [4]辽宁省沈阳市第十人民医院

出　　处：《河北医药》2024年第19期2898-2903,共6页Hebei Medical Journal

基　　金：辽宁省自然科学基金项目(编号:2019-221);沈阳市科技计划项目(编号:19-112-4-040)。

摘　　要：目的 探索miR-137-5p对阿尔茨海默病(AD)的保护机制。方法 首先用qRT-PCR评估AD患者和健康对照组人血清中miR-137和USP30的表达。用D-半乳糖和氯化铝建立AD小鼠模型,用水迷宫试验检测小鼠的行为,确认AD小鼠模型的成功。用Aβ1-42寡聚体诱导的SH-SY5Y细胞建立AD细胞模型,通过实时定量聚合酶链反应检测AD模型中miR-137-5p和USP30的表达。双重荧光素酶试验用于验证miR-137-5p和USP30之间的靶向结合关系。结果 miR-137-5p的表达在AD患者中与健康对照组相比有所下降(P<0.05),而USP30则明显增加(P<0.05)。miR-137-5p能改善AD细胞模型中的细胞凋亡,USP30的过表达部分废除了miR-137-5p对Aβ1-42-处理的SH-SY5Y细胞的影响,miR-137-5p通过靶向USP30改善AD小鼠的认知能力和Aβ的沉积。结论 miR-137-5p可以通过下调USP30来改善AD症状,miR-137-5p可能能成为治疗AD的一个靶点。Objective To explore the protective mechanism of miR-137-5p in Alzheimer’s disease(AD).Methods The expressions of miR-137 and ubiquitin specific protease 30(USP30)in serum samples of AD patients and healthy controls were measured by quantitative reverse transcriptase PCR(qRT-PCR).The AD mouse model was established with D-galactose and aluminum chloride,which was verified by the water maze test to assess mouse behaviors.An in vitro AD model was created in amyloid beta 1-42(Aβ1-42)oligomer-induced SH-SY5Y cells,and the expressions of miR-137-5p and USP30 in the AD model were detected by qRT-PCR.Dual-luciferase reporter assay was performed to verify the target binding relationship between miR-137-5p and USP30.Results MiR-137-5p was downregulated in AD patients compared with that of healthy controls(P<0.05),while USP30 was significantly upregulated(P<0.05).MiR-137-5p improved apoptosis in the in vitro AD model,and overexpression of USP30 partially reversed the regulatory effect of miR-137-5p on Aβ1-42-induced SH-SY5Y cells.MiR-137-5p improved cognitive performance and Aβdeposition in AD mice through targeting USP30.Conclusion MiR-137-5p can improve AD symptoms by down-regulating USP30,suggesting that miR-137-5p can be a therapeutic target for the treatment of AD.

关 键 词：阿尔茨海默病 miR-137-5p USP30 AΒ1-42 

分 类 号：R749.16[医药卫生—神经病学与精神病学]