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衰老加速小鼠中STUB1的年龄相关表达及其对抗阿尔茨海默病中药的反应

Age-related expression of STUB1 in senescence-accelerated mice and its response to anti-Alzheimer's disease traditional Chinese medicine.

作者信息

Zhang Gui-Rong, Cheng Xiao-Rui, Zhou Wen-Xia, Zhang Yong-Xiang

机构信息

Beijing Institute of Pharmacology and Toxicology, Beijing 100850, China.

出版信息

Neurosci Lett. 2008 Jun 27;438(3):371-5. doi: 10.1016/j.neulet.2008.04.075. Epub 2008 Apr 25.

Abstract

Increasing evidences have indicated that STUB1 may be closely linked to Alzheimer's disease (AD). Senescence-accelerated mice (SAM) prone/8 (SAMP8) is a generally acknowledged animal model for senescence and AD, and SAM resistant/1 (SAMR1) is its control. In this study, we investigated the detailed expression of STUB1 in the brain of SAMP8 with aging and its responses to five anti-AD traditional Chinese medicinal (TCM), using real-time fluorescence quantitative PCR and Western blot technique. Results showed that with the aging process, both mRNA and protein expression of STUB1 in the cerebral cortex and hippocampus from SAMR1 increased after 2 months, while they decreased in brain tissues from SAMP8 after 6 months. Compared with SAMR1, the mRNA and protein expression of STUB1 decreased after 10 months in SAMP8 but could be up-regulated by the five anti-AD TCM used in this study. These results indicated that the expression of STUB1 in the brain of SAMP8 was abnormal and this abnormality could be reversed by anti-AD TCM. The data suggested that a deficiency in STUB1 may lead to a reduction in aberrant protein scavenging, causing abnormal protein accumulation in the brain of SAMP8. Thus, STUB1 might be a potential target for anti-AD TCM.

摘要

越来越多的证据表明,STUB1可能与阿尔茨海默病(AD)密切相关。快速老化小鼠(SAM)易感性/8(SAMP8)是一种公认的衰老和AD动物模型,而SAM抗性/1(SAMR1)是其对照。在本研究中,我们采用实时荧光定量PCR和蛋白质印迹技术,研究了衰老过程中SAMP8脑内STUB1的详细表达情况及其对五种抗AD中药的反应。结果显示,随着衰老进程,SAMR1大脑皮质和海马中STUB1的mRNA和蛋白表达在2个月后升高,而SAMP8脑组织中其表达在6个月后降低。与SAMR1相比,SAMP8中STUB1的mRNA和蛋白表达在10个月后降低,但可被本研究中使用的五种抗AD中药上调。这些结果表明,SAMP8脑内STUB1的表达异常,且这种异常可被抗AD中药逆转。数据提示,STUB1缺乏可能导致异常蛋白清除减少,致使SAMP8脑内异常蛋白蓄积。因此,STUB1可能是抗AD中药的潜在靶点。

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