摘要
阿尔兹海默症是一种与年龄相关的退行性疾病,以Aβ沉积形成斑块、Tau蛋白过度磷酸化形成神经纤维缠结为主要病理表现。黄酮类化合物是一种自然界广泛存在的次级代谢产物,具有神经保护作用。该研究以冈田酸(OA)诱导人神经母细胞瘤SH-SY5Y建立Tau蛋白过度磷酸化的AD体外细胞模型,基于该细胞模型对青藏高原特色植物中的黄酮类化合物进行体外抗AD活性的研究。利用Western blot检测Ser^(396)位点的磷酸化水平,评价黄酮类化合物对该模型的保护作用。并利用上述AD模型研究筛选得到的黄酮类化合物对线粒体功能(活性氧和膜电势)以及相关蛋白表达水平的影响。研究结果表明,筛选得到的有效化合物芫花素(T8)可通过降低Tau蛋白过度磷酸化、改善线粒体功能障碍和降低细胞内ROS等方面起到神经保护作用,对进一步开发预防或治疗AD药物研究提供实验依据。
Alzheimer’s disease(AD)is neurodegenerative disease related to age,and its main pathological features are senile plaques formed by the deposition ofβ-amyloid(Aβ)and neurofibrillary tangles(NFT)formed by hyperphosphorylated Tau.Flavonoids are secondary metabolite,existing widely in the nature.The study used okadaic acid(OA)-induced SH-SY5Y cells to build Tau hyperphosphorylation of AD model in vitro,and based on the AD model in vitro to investigate the protective effect of flavonoids on Tau hyperphosphorylation and to explore its possible mechanism.The phosphorylation level at Ser^(396) was detected by Western blot to evaluate the protective effect of flavonoids on the model in vitro.The AD model above was used to study the influence of the screened flavonoids on mitochondrial function(ROS and membrane potential)and Western blot was used to detect the expression level of related protein.The results showed that superior compounds Genkwanin(T8)can play an important neuroprotective role by reducing Tau protein hyperphosphorylation,improving mitochondrial dysfunction,reducing intracellular ROS.It provides experimental basis for further research on the development of drugs for the prevention or treatment of AD.
作者
王洪伦
付洋洋
铁芳芳
Wang Honglun;Fu Yangyang;Tie Fangfang(Northwest Institute of Plateau Biology,CAS,Key Laboratory of Tibetan Medicine Research,CAS,Xining 810008,China;Qinghai Provincal Key Laboratory of Tibetan Medicine Research,Xining 810008,China)
出处
《青海科技》
2023年第4期46-55,共10页
Qinghai Science and Technology
基金
青海省自然科学基金面上项目(2020-ZJ-905)。
