多功能蛋白p62在阿尔茨海默病大鼠脑组织tau过磷酸化中的作用机制研究

发布时间：2018-06-07 11:24

本文选题：Alzheimer + disease　；参考：《吉林大学》2012年博士论文

【摘要】：阿尔茨海默病（AD)是最多见的脑变性疾病,主要病理变化为老年斑(SP)和神经纤维缠结(NFT)及神经元丢失。NFT主要由过磷酸化tau缠结后形成，与AD脑组织神经元减少直接相关。适度的细胞自噬被认为是细胞保护机制。但自噬与神经元变性疾病之间的关系有待阐明。正常神经元几乎不存在自噬体，，自噬升高可引起神经元凋亡和变性。多功能蛋白p62作为受体参与选择性自噬。研究表明，AD脑组织NFT中存在p62，推测自噬及受体p62可能参与tau过磷酸化,但其机制不清楚。本实验复制了-淀粉样蛋白和半乳糖协同诱导的AD大鼠模型，通过研究脑组织自噬、p62与Keap1-Nrf2-ARE相关蛋白发现AD模型鼠脑组织自噬水平升高清除p62蛋白；导致Nrf2-ARE通路抗氧化能力不足而促进tau过磷酸化生成增加是引起AD神经元形态及功能障碍的原因之一。
[Abstract]:Alzheimer's disease (AD) is one of the most common brain degeneration diseases. The main pathological changes of AD are neurofibrillary tangles (NFT) and neuronal loss. NFT is mainly formed after hyperphosphorylation of tau tangles, which is directly related to the decrease of neurons in AD brain tissue. Moderate autophagy is thought to be the mechanism of cell protection. However, the relationship between autophagy and neuronal degeneration needs to be clarified. There is almost no autophagy in normal neurons, and increased autophagy can induce apoptosis and degeneration of neurons. Multifunctional protein p62 is involved in selective autophagy as a receptor. It is suggested that there is p62 in NFT of AD brain, suggesting that autophagy and p62 may be involved in tau hyperphosphorylation, but the mechanism is not clear. In this study, the AD rat model induced by -amyloid protein and galactose was established. Through the study of brain autophagy p62 and Keap1-Nrf2-ARE related proteins, it was found that the level of autophagy in brain tissue of AD model was increased and p62 protein was removed. The increase of tau hyperphosphorylation due to the insufficiency of antioxidant capacity in Nrf2-ARE pathway is one of the causes of the morphological and functional disorders of AD neurons.
【学位授予单位】：吉林大学
【学位级别】：博士
【学位授予年份】：2012
【分类号】：R749.16

【共引文献】