托芬那酸：一种tau蛋白修饰剂及其在认知和tau蛋白病中的作用。
Tolfenamic Acid: A Modifier of the Tau Protein and its Role in Cognition and Tauopathy.
作者信息
Chang Joanna K, Leso Allison, Subaiea Gehad M, Lahouel Asma, Masoud Anwar, Mushtaq Foqia, Deeb Reem, Eid Aseel, Dash Miriam, Bihaqi Syed W, Zawia Nasser H
机构信息
Department of Biomedical and Pharmaceutical Sciences, University of Rhode Island, Kingston, RI, United States.
Interdisciplinary Neuroscience Program, University of Rhode Island, Kingston, RI, United States.
出版信息
Curr Alzheimer Res. 2018;15(7):655-663. doi: 10.2174/1567205015666180119104036.
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.
背景
缠结是过度磷酸化tau蛋白的沉积物，在多种被称为tau蛋白病的神经退行性疾病中均可发现，其中阿尔茨海默病（AD）最为常见。tau蛋白病的临床特征为痴呆，并具有由tau蛋白聚集体构成的共同皮质病变。
目的
在本研究中，我们探讨了托芬那酸（TA）在携带人类tau基因（hTau）的转基因动物模型中改善疾病进程的治疗潜力。
方法
采用行为测试、蛋白质印迹法和免疫组织化学分析来证明TA的疗效。
结果
TA治疗改善了年轻和老年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显示，给予TA后，总tau蛋白以及tau蛋白位点特异性过度磷酸化均减少。对磷酸化tau蛋白的免疫组织化学分析显示，接受TA治疗的动物额叶皮质、海马体和纹状体中的染色减少。
结论
TA有潜力作为一种疾病修饰剂用于治疗包括AD在内的tau蛋白病。
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