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Specific Degradation of Endogenous Tau Protein and Inhibition of Tau Fibrillation by Tanshinone IIA through the Ubiquitin-Proteasome Pathway.
Journal of Agricultural and Food Chemistry ( IF 5.7 ) Pub Date : 2020-02-07 , DOI: 10.1021/acs.jafc.9b07022 Nan Cai 1, 2 , Jiajie Chen 3 , Decheng Bi 1 , Liang Gu 1 , Lijun Yao 1 , Xiuting Li 4 , Hui Li 1 , Hong Xu 1 , Zhangli Hu 1 , Qiong Liu 1 , Xu Xu 1
Journal of Agricultural and Food Chemistry ( IF 5.7 ) Pub Date : 2020-02-07 , DOI: 10.1021/acs.jafc.9b07022 Nan Cai 1, 2 , Jiajie Chen 3 , Decheng Bi 1 , Liang Gu 1 , Lijun Yao 1 , Xiuting Li 4 , Hui Li 1 , Hong Xu 1 , Zhangli Hu 1 , Qiong Liu 1 , Xu Xu 1
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Alzheimer's disease (AD) is a common neurodegenerative disease which is partly characterized by the aggregation of hyperphosphorylated Tau proteins forming neurofibrillary tangles that promote AD pathogenesis. In this study, we investigated the effects of tanshinone IIA (Tan IIA) isolated from Salvia miltiorrhiza on Tau degradation in the treatment of AD. The results showed that Tan IIA reduced the Tau expression and attenuated Tau phosphorylation in N2a cells, Tau-overexpressing cells, and 3×Tg-AD mouse primary neuron cells. Moreover, Tan IIA increased polyubiquitinated Tau accumulation and induced proteasomal degradation of the Tau protein. Additionally, Tan IIA became bound to the Tau protein and inhibited the formation of heparin-induced Tau fibrils. In summary, Tan IIA can increase polyubiquitinated Tau accumulation and induce the proteasomal degradation of the Tau protein and the binding of Tan IIA to the Tau protein, inhibiting the formation of Tau fibrils. Tan IIA may be further explored as a potential candidate for AD treatment.
中文翻译：
丹参酮IIA通过泛素-蛋白酶体途径特异性降解内源性Tau蛋白和抑制Tau纤颤。
阿尔茨海默氏病（AD）是一种常见的神经退行性疾病，其部分特征在于高磷酸化Tau蛋白的聚集，形成了促进AD发病机理的神经原纤维缠结。在这项研究中，我们调查了从丹参中分离的丹参酮IIA（Tan IIA）对AD治疗中Tau降解的影响。结果表明，Tan IIA在N2a细胞，Tau过表达细胞和3xTg-AD小鼠原代神经元细胞中降低Tau表达并减弱Tau磷酸化。此外，Tan IIA增加了泛素化的Tau积累并诱导了Tau蛋白的蛋白酶体降解。此外，Tan IIA与Tau蛋白结合并抑制了肝素诱导的Tau原纤维的形成。综上所述，Tan IIA可以增加多泛素化Tau的积累，并诱导Tau蛋白的蛋白酶体降解以及Tan IIA与Tau蛋白的结合，从而抑制Tau原纤维的形成。Tan IIA可能会进一步探讨作为AD治疗的潜在候选人。
更新日期：2020-02-07
中文翻译：
丹参酮IIA通过泛素-蛋白酶体途径特异性降解内源性Tau蛋白和抑制Tau纤颤。
阿尔茨海默氏病（AD）是一种常见的神经退行性疾病，其部分特征在于高磷酸化Tau蛋白的聚集，形成了促进AD发病机理的神经原纤维缠结。在这项研究中，我们调查了从丹参中分离的丹参酮IIA（Tan IIA）对AD治疗中Tau降解的影响。结果表明，Tan IIA在N2a细胞，Tau过表达细胞和3xTg-AD小鼠原代神经元细胞中降低Tau表达并减弱Tau磷酸化。此外，Tan IIA增加了泛素化的Tau积累并诱导了Tau蛋白的蛋白酶体降解。此外，Tan IIA与Tau蛋白结合并抑制了肝素诱导的Tau原纤维的形成。综上所述，Tan IIA可以增加多泛素化Tau的积累，并诱导Tau蛋白的蛋白酶体降解以及Tan IIA与Tau蛋白的结合，从而抑制Tau原纤维的形成。Tan IIA可能会进一步探讨作为AD治疗的潜在候选人。
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