本文選題：Alzheimer + disease��； 參考：《吉林大學》2012年博士論文

【摘要】：阿爾茨海默�。ˋD)是最多見的腦變性疾病,主要病理變化為老年斑(SP)和神經纖維纏結(NFT)及神經元丟失。NFT主要由過磷酸化tau纏結后形成，與AD腦組織神經元減少直接相關。 適度的細胞自噬被認為是細胞保護機制。但自噬與神經元變性疾病之間的關系有待闡明。正常神經元幾乎不存在自噬體，，自噬升高可引起神經元凋亡和變性。多功能蛋白p62作為受體參與選擇性自噬。研究表明，AD腦組織NFT中存在p62，推測自噬及受體p62可能參與tau過磷酸化,但其機制不清楚。 本實驗復制了-淀粉樣蛋白和半乳糖協同誘導的AD大鼠模型，通過研究腦組織自噬、p62與Keap1-Nrf2-ARE相關蛋白發(fā)現AD模型鼠腦組織自噬水平升高清除p62蛋白；導致Nrf2-ARE通路抗氧化能力不足而促進tau過磷酸化生成增加是引起AD神經元形態(tài)及功能障礙的原因之一。
[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.
【學位授予單位】：吉林大學
【學位級別】：博士
【學位授予年份】：2012
【分類號】：R749.16

【共引文獻】

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