摘要
背景:缠结是过度磷酸化tau的沉积物,其在多种神经退行性疾病中发现,称为tau蛋白病,其中阿尔茨海默病(AD)是最常见的。 Tau蛋白病在临床上以痴呆为特征,并共有由蛋白质tau聚集体组成的常见皮质损伤。 目的:在本研究中,我们探索了托芬那酸(TA)在修饰携带人tau基因(hTau)的转基因动物模型中的疾病过程中的治疗潜力。 方法:行为学检测,蛋白质印迹法和免疫组织化学分析用于证明TA的疗效。 结果:TA治疗改善了年轻和年老的hTau小鼠的空间学习缺陷和记忆障碍。对hTau蛋白的蛋白质印迹分析揭示总τ的减少以及响应于TA给药的tau的位点特异性超磷酸化。磷酸化tau蛋白的免疫组织化学分析显示用TA治疗的动物在额皮质,海马和纹状体中染色减少。 结论:TA具有作为治疗包括AD在内的tau蛋白病的疾病修饰剂的潜力。
关键词: 阿尔茨海默氏病,托芬那酸,hTau小鼠模型,tau蛋白病,微管相关蛋白Tau(MAPT),痴呆。
Current Alzheimer Research
Title:Tolfenamic Acid: A Modifier of the Tau Protein and its Role in Cognition and Tauopathy
Volume: 15 Issue: 7
关键词: 阿尔茨海默氏病,托芬那酸,hTau小鼠模型,tau蛋白病,微管相关蛋白Tau(MAPT),痴呆。
摘要: Background: Tangles are deposits of hyperphosphorylated tau, which are found in multiple neurodegenerative disorders that are referred to as tauopathies, of which Alzheimer's disease (AD) is the most common. Tauopathies are clinically characterized by dementia and share common cortical lesions composed of aggregates of the protein tau.
Objective: In this study, we explored the therapeutic potential of tolfenamic acid (TA), in modifying disease processes in a transgenic animal model that carries the human tau gene (hTau).
Methods: Behavioral tests, Western blotting and Immunohistochemical analysis were used to demonstrate the efficacy of TA.
Results: Treatment of TA improved improving spatial learning deficits and memory impairments in young and aged hTau mice. Western blot analysis of the hTau protein revealed reductions in total tau as well as in sitespecific hyperphosphorylation of tau in response to TA administration. Immunohistochemical analysis for phosphorylated tau protein revealed reduced staining in the frontal cortex, hippocampus, and striatum in animals treated with TA.
Conclusion: TA holds the potential as a disease-modifying agent for the treatment of tauopathies including AD.
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Cite this article as:
Tolfenamic Acid: A Modifier of the Tau Protein and its Role in Cognition and Tauopathy, Current Alzheimer Research 2018; 15 (7) . https://dx.doi.org/10.2174/1567205015666180119104036
DOI https://dx.doi.org/10.2174/1567205015666180119104036 |
Print ISSN 1567-2050 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5828 |
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