Specific Degradation of Endogenous Tau Protein and Inhibition of Tau Fibrillation by Tanshinone IIA through the Ubiquitin-Proteasome Pathway.
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| Abstract |
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.
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| Authors | Nan Cai, Jiajie Chen, Decheng Bi, Liang Gu, Lijun Yao, Xiuting Li, Hui Li, Hong Xu, Zhangli Hu, Qiong Liu, Xu Xu |
| Journal | Journal of agricultural and food chemistry (J Agric Food Chem) Vol. 68 Issue 7 Pg. 2054-2062 (Feb 19 2020) ISSN: 1520-5118 [Electronic] United States |
| PMID | 31995984 (Publication Type: Journal Article) |
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