| First Author | Kim S | Year | 2022 |
| Journal | Biomed Pharmacother | Volume | 156 |
| Pages | 113865 | PubMed ID | 36242849 |
| Mgi Jnum | J:358338 | Mgi Id | MGI:7397965 |
| Doi | 10.1016/j.biopha.2022.113865 | Citation | Kim S, et al. (2022) Dual modulators of aggregation and dissociation of amyloid beta and tau: In vitro, in vivo, and in silico studies of Uncaria rhynchophylla and its bioactive components. Biomed Pharmacother 156:113865 |
| abstractText | A prominent characteristic of Alzheimer's disease (AD) is the deposition of both amyloid-beta (Abeta) peptide and tau protein in the brain. Abeta and tau not only induce toxicity through self-aggregation but also induce more potent toxicity through the synergistic action of Abeta and tau. In particular, neurotoxic aggregates of Abeta and tau directly affect several AD pathologies including neuroinflammation and cognitive decline. Therefore, there is increasing interest in strategies to modulate the aggregation and dissociation of Abeta and tau for treatment of AD. Our recent study found that Uncaria rhynchophylla (UR) has a therapeutic effect on AD via the inhibition of Abeta aggregation and attenuating Abeta-mediated pathogenesis of AD. However, no studies have investigated whether UR has anti- and disaggregation effects on both Abeta and tau. In this study, we showed the significant effects of UR on aggregation and dissociation of Abeta(42) and tau K18 using a thioflavin T (ThT) assay. In addition, histological study revealed an inhibitory effect of UR on the accumulation of Abeta and tau and AD-related pathologies in 3xTg mice with both Abeta and tau pathology. Furthermore, we found that rhynchophylline and corynoxeine, bioactive components of UR, could modulate the aggregation and dissociation of both Abeta and tau using molecular docking simulation, isothermal titration calorimetry, and ThT assays. In conclusion, our results demonstrate that UR can inhibit the aggregation of Abeta and tau and promote the degradation of their aggregates in AD. |
