基于LncRNA调控Aβ诱导自噬探讨维生素D3对阿尔茨海默病作用机制

Previous research has suggested that an association exists between vitamin D3 and the pathology of Alzheimer’s disease (AD); however, the mechanism of action remains unclear. In this study, we explored the intervention effect and action mechanism of vitamin D3 on AD based on the autophagy pathway induced by amyloid beta (Aβ) via long non-coding RNA (lncRNA) regulation in 3 models: cell, animal, and population. Abnormal LncRNA identified，APP、BACE-1、PPARγ、autophagy related biomarkers（Beclin-1、AMPK、LC3-I和LC3-Ⅱ） are selected as biomarkers. The changes of mRNA expression and protein levels were tested before and after intervention of vitamin D3. On this basis, the level of autophagy induced by different doses of Aβ can be determined.The role of the autophagy pathway induced by Aβ via LncRNA in AD pathogensis can be proved.The effects of vitamin D3 on different stages of AD and the exact target site on this pathway will be further clarified. The results will provide scientific evidence for exploring molecular markers in AD diagnosis, treatment, and prognosis. These results are further expected to provide a novel epigenetic method to explore the molecular mechanisms underlying AD development, thereby opening new paths for the prevention and treatment of neurodegenerative diseases.

本研究基于国内外研究现状、相关理论和我们前期研究基础，从阿尔茨海默病（Alzheimer’desease ，AD）细胞、动物和人群三个层面探讨基于LncRNA调控Aβ诱导自噬途径在AD发生中的作用及维生素D3对上述途径的干预效果。通过检测维生素D3干预前后AD细胞、动物模型及AD、MCI患者已鉴定差异LncRNA、APP、BACE-1、PPARγ及自噬相关标志物（Beclin-1、AMPK、LC3-I和LC3-Ⅱ）的mRNA表达水平及上述蛋白水平变化。探讨不同Aβ剂量对自噬诱发程度，自噬途径在AD发生不同阶段中的作用，以及基于LncRNA调控Aβ诱导自噬途径在AD发生过程中作用，明确维生素D3在此路径的作用靶点及效果，为寻找AD诊断、治疗及预后相关分子标志物提供新思路，为探讨AD发生发展的分子机制提供表观遗传信息，为神经退行性疾病防治开辟新途径。