新穎性修飾於血清類澱粉蛋白在阿茲海默症致病角色之探討

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題名:	新穎性修飾於血清類澱粉蛋白在阿茲海默症致病角色之探討 The investigation of Novel Modifications on Serum Amyloid Beta in the Pathogenesis of Alzheimer Disease
作者:	甘淑儀 Kam, Rachel Sook-Yee
貢獻者:	醫學檢驗暨生物技術學系所林詠峰
關鍵詞:	阿茲海默症;類澱粉前驅蛋白;丙烯醛;β-類澱粉胜肽;轉譯後修飾 beta-Amyloid;Amyloid Precursor Protein;Acrolein;Post-translational modification
日期:	2019-06-13
上傳時間:	2020-02-25 10:00:15 (UTC+8)
摘要:	阿茲海默症(Alzheimer’s disease, AD)為一種漸進式神經退化性疾病, 並且是最常見的失智症形態，其主要病徵為神經纖維糾結以及類澱粉蛋白斑塊 (Amyloid plaques) 之堆積。β-類澱粉胜肽(Aβ)由類澱粉前驅蛋白(APP)的切割衍生而成。許多研究支持Aβ 為AD 的致病因素，並認為它是必要的，但不足以完全解釋該疾病的發病機制，故仍有待更深入地澄清。丙烯醛(Acrolein, ACR)是脂質的過氧化物之一，廣泛存在於環境中的污染物，是極強的親電性化合物，形成蛋白質加成物 (acrolein-protein adducts) ，是蛋白質轉譯後修飾(Post-translational modification, PTM)的一種。本研究使用酵素連結免疫分析法偵測到AD 患者和健康對照者HC 的血清樣本中Aβ 的含量沒有差異，也都有丙烯醛加成物的存在；進一步使用合成的Aβ 片段，一部分以acrolein 修飾，檢測出相關的自體抗體在AD 血清中增加，表示Aβ 和acrolein 加成物的自體抗體對於AD 的病理發展有顯著的影響。為了深入獲得Aβ 相關的AD 病理學機制，我們構建了用於細胞研究的APP 質體。可在不久的將來揭示該疾病進展的更多細節。在AD 血清中增加，表示Aβ 和 acrolein 加成物的自體抗體對於AD 的病理發展有顯著的影響。為了深入獲得Aβ 相關的AD 病理學機制，我們構建了用於細胞研究的APP 質體。可在不久的將來揭示該疾病進展的更多細節。 Alzheimer's disease (AD) is a progressive neurodegenerative disease and is the most common form of dementia. Its key pathological hallmarks are accumulation of amyloid plaques and neurofibrillary tangles. The β-amyloid peptide (Aβ) is derived from the cleavage of amyloid precursor protein (APP). Many studies support Aβ as the causative factor of AD and consider it necessary, but not enough to fully explain the pathogenesis of the disease, so it remains to be further clarified. Acrolein is one of the by-products of lipid peroxidation. Due to its high reactivity, it is also an initiator of oxidative stress by adducting cellular nucleophilic groups. In the brains of AD patients, levels of acrolein are significantly higher in the vulnerable brain regions. To search for potential early biomarkers of AD, we analyzed the serum of AD patients using ELISA in comparison to that of healthy control (HC) subjects with a focus on post-translational modifications including acrolein and related antibodies. We found no difference in Aβ content in serum samples between AD patients and HC subjects. Acrolein adducts were also present in the serum of both groups. We further used synthetic Aβ fragments, a portion of which was modified with acrolein. It is striking that associated autoantibodies were increased in AD serum, indicating that autoimmunity related to Aβ and acrolein adducts has a significant influence on the pathological development of AD. To get insights of AD pathology involving Aβ, we constructed APP plasmids for cellular studies. More details of the disease progression may be revealed in the near future.
描述:	碩士指導教授：林詠峰委員：林子暘委員：高淑慧
資料類型:	thesis
顯示於類別:	[醫學檢驗暨生物技術學系所] 博碩士論文

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