Specific Degradation of Endogenous Tau Protein and Inhibition of Tau Fibrillation by Tanshinone IIA through the Ubiquitin- Proteasome Pathway
Specific Degradation of Endogenous Tau Protein and Inhibition of Tau Fibrillation by Tanshinone IIA through the Ubiquitin- Proteasome Pathway
复制标题
丹参酮 IIA 通过泛素-蛋白酶体途径特异性降解内源 Tau 蛋白并抑制 Tau 纤维颤动
DOI：
10.1021/acs.jafc.9b07022
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发表时间：
2020-02-19
影响因子：
6.1
通讯作者：
Xu, Xu
中科院分区：
文献类型：
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作者：
Cai, Nan;Chen, Jiajie;Xu, Xu
阿尔茨海默病（AD）是一种常见的神经退行性疾病，其部分特征在于过度磷酸化的Tau蛋白聚集形成促进AD发病的神经元缠结。在这项研究中，我们研究了从丹参中分离的丹参酮IIA（Tan IIA）在治疗AD中对Tau降解的影响。结果显示，Tan IIA降低了N2 a细胞、Tau过表达细胞和3xTg-AD小鼠原代神经元细胞中的Tau表达并减弱了Tau磷酸化。此外，Tan IIA增加了多泛素化Tau的积累，并诱导Tau蛋白的蛋白酶体降解。此外，Tan IIA与Tau蛋白结合并抑制肝素诱导的Tau原纤维的形成。总之，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和Tan IIA与Tau蛋白的结合，抑制Tau原纤维的形成。Tan IIA可进一步探索作为AD治疗的潜在候选药物。
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 3xTg-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.