A state-of-the-art review on miRNA in prevention and treatment of Alzheimer 's disease / 浙江大学学报·医学版

Alzheimer's disease (AD) is a multifactorial and heterogenic disorder. MiRNA is a class of non-coding RNAs with 19-22 nucleotides in length that can regulate the expression of target genes in the post-transcriptional level. It has been found that the miRNAome in AD patients is significantly altered in brain tissues, cerebrospinal fluid and blood circulation, as compared to healthy subjects. Experimental studies have suggested that expression changes in miRNA could drive AD onset and development via different mechanisms. Therefore, targeting miRNA expression to regulate the key genes involved in AD progression is anticipated to be a promising approach for AD prevention and treatment. Rodent AD models have demonstrated that targeting miRNAs could block biogenesis and toxicity of amyloid β, inhibit the production and hyper-phosphorylation of τ protein, prevent neuronal apoptosis and promote neurogenesis, maintain neural synaptic and calcium homeostasis, as well as mitigate neuroinflammation mediated by microglia. In addition, animal and human studies support the view that miRNAs are critical players contributing to the beneficial effects of cell therapy and lifestyle intervention to AD. This article reviews the most recent advances in the roles, mechanisms and applications of targeting miRNA in AD prevention and treatment based on rodent AD models and human intervention studies. The potential opportunities and challenges in clinical application of targeting miRNA for AD patients are also discussed.

Screening of 14-3-3τ protein inhibitors from natural products based on fluorescence spectroscopy, surface plasmon resonance and molecular docking technique / 国际药学研究杂志

Objective:To study and establish a method for the efficient screening of 14-3-3τ protein inhibitors from natural products, and analyze the sites of their interactions with the 14-3-3τ protein. Methods: The binding activity of natural compounds with the 14-3-3τ protein was tested by the liquid chromatography-fluorescence spectroscopy, and the binding activity of the potential compounds was further verified by the surface plasmon resonance(SPR)technique. The binding sites of the active compounds were predicted by the molecular docking technique. Furthermore, the key binding sites were selected and then validated using amino acid site-directed mutants. Results: A total of 17 different type compounds with potential 14-3-3τ binding activity were screened out from 82 natural products. The binding activi- ties of 10 compounds were verified by the SPR experiments. Then the binding sites of interactions between the 14-3-3τ protein and the 10 compounds were predicted by the molecular docking technology to be mainly at the Arg56, Arg127 and Y128A, dem- onstrate that the binding of five of the 10 compounds with the target protein was associated with the three sites Arg56, Arg127 and Tyr128. Conclusion: The established method is accurate and efficient, which could be used for rapid screening of small molecule 14-3-3τ inhibitors from natural products. The present study provides a reference and a new approach for the rapid screening of 14-3-3τ inhibitors for the new breast cancer therapeutic drugs.