中国医学科学院医学实验动物研究所,北京协和医学院比较医学中心,国家卫生健康委员会人类疾病比较医学重点实验室, 国家人类疾病动物模型资源库,北京市人类重大疾病实验动物模型工程技术研究中心,北京 100021
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中国医学科学院医学与健康科技创新工程 (2019-12M-1-004) 资助项目.
(Institute of Laboratory Animal Science, Chinese Academy of Medical Science (CAMS); Comparative Medicine Center, Peking Union Medical College (PUMC); NHC Key Laboratory of Human Disease Comparative Medicine; National Human Disease Animal Model Resource Center; Beijing Engineering Research Center for Experimental Animal Models of Human Critical Disease, Beijing 100021, China)
This work was supported by a grant from Chinese Academy of Medical Sciences (CAMS) Innovation Fund for Medical Sciences(2019-12M-1-004).
随着全球老龄化日益严重, 阿尔茨海默病 (Alzheimer’s disease,AD)作为神经退行性疾病的最常见类型,以进行性认知障碍为主要临床表现,以老年斑、神经纤维缠结和神经元及突触的凋亡缺失为主要病理特征. 细胞凋亡抑制家族蛋白 (inhibitor of apoptosis family protein,IAP)是一类内源性细胞凋亡抑制蛋白,它们在AD病理进程中的功能尚未十分明确. 本研究从AD患者数据库、动物模型和诱导的脑片模型分析IAPs蛋白表达,并通过EMSA和免疫印迹实验初步探索了NFκB信号通路的活化. 结果表明:存活蛋白(Survivin)在AD患者、小鼠模型以及Aβ、冈田酸和LPS诱导脑片中共同上调,同时NFκB通路被显著激活,两者变化趋势相似,可能通过NFκB-Survivin轴抵抗神经元凋亡. Survivin蛋白在AD中的进一步深入研究将成为AD治疗和预防的重要靶标.
As the increasing aging population globally, Alzheimer’s disease (AD) has been the most common type of neurodegenerative disease, characterized with progressive cognitive impairment. The main pathological features were senile plaques, neurofibrillary tangles and neurons and synapse loss. Inhibitor of apoptosis family proteins (IAPs) are a class of endogenous apoptosis inhibitors, and their function in the pathological process of AD has not been clear. In this study, IAPs protein expression were analyzed from AD patient databases, AD animal models and brain slice models. NFκB signaling pathway was detected by EMSA and immunoblotting. The results show that Survivin acts as a co-upregulated gene in all models including AD patients, AD mouse models and Aβ, okadaic acid and LPS induced brain slices. NFκB signaling pathway was significantly activated, and they exhibited the similar expression profile. Therefore, the cell apoptosis in AD progression may be inhibited by NFκB/IAPs axis. Survivin may be an important target for AD prevention and treatment.
路亚岚,周澧,韩云林,王克维,秦川.细胞凋亡抑制家族蛋白在阿尔茨海默病动物模型中的表达及其初步作用机制研究[J].生物化学与生物物理进展,2021,48(8):898-906
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