澱粉樣胜肽β寡聚體在脂質膜上形成孔道之濃度測量;The Measurement of Critical Concentration to Form Amyloid Pore in Membrane by Amyloid Beta Oligomer

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题名:	澱粉樣胜肽β寡聚體在脂質膜上形成孔道之濃度測量;The Measurement of Critical Concentration to Form Amyloid Pore in Membrane by Amyloid Beta Oligomer
作者:	陳佳宏;Chen, Chia-Hung
贡献者:	化學工程與材料工程學系
关键词:	β-澱粉樣胜肽寡聚體;離子通道;濃度
日期:	2020-08-17
上传时间:	2020-09-02 15:14:28 (UTC+8)
出版者:	國立中央大學
摘要:	β-澱粉樣胜肽寡聚體形成之離子通道被認為是誘發阿茲海默症的重要原因。此種類型之離子通道會破壞細胞內之鈣離子平衡，並導致神經細胞死亡。離子通道的生成取決於胜肽的濃度以及細胞膜本身之不飽和程度。目前仍沒有研究去測量胜肽形成離子通道的絕對濃度，然而測量此濃度卻是重要的。因為β-澱粉樣胜肽寡聚體較容易與不飽和度高的細胞膜結合並形成孔道。大腦灰質之異常一直以來被視為是阿茲海默症的最主要病因，然而近期有關治療大腦灰質之藥物開發以及實驗研究都沒辦法有效的治癒或者是延緩阿茲海默症的症狀，所以有另一部份學者認為大腦白質之異常是誘發阿茲海默症之另一種重要病因，因大腦白質之細胞膜含有最高的不飽和度，所以我們想從此研究中以β-澱粉樣胜肽寡聚體誘發孔洞形成之觀點來解釋大腦白質異常是阿茲海默症中的一種重要病因。在此研究中，我們發現形成離子通道所需之絕對濃度在不飽和度較高的細胞膜中比較低，且我們同時發現當加入β-澱粉樣胜肽寡聚體時細胞膜之結構會有明顯改變。最終結果闡明了β-澱粉樣胜肽寡聚體誘發孔洞形成可能是大腦白質異常之中的分子機制以及是阿茲海默症的一種重要病因。 ;Formation of the ion channels on neuronal membranes by the amyloid beta (Aβ) oligomers is recently considered as the potential pathogenic origin of the Alzheimer’s disease (AD). These ion channels will break the balance of calcium ions across the membranes and thereby kill the neurons. The pore formation process is concentration- and membrane composition-dependent. But none of the existing studies systematically measured the critical concentrations and their composition dependence for the ion channel formation by the Aβ oligomers. Given that the abnormality on the white matter of human brains is believed to be a key factor in the AD pathogenesis and that the neuronal membranes in the white matter contain the lipids of higher unsaturation degrees, figuring out how the critical concentration of the ion channel formation correlates with the membrane composition may elucidate the molecular mechanism underlying the pathogenic involvement in AD of the white matter. In this study, we used lipids with different unsaturation degrees to construct the model membrane systems and to mimic the different unsaturation degrees between the white matter and grey matter of human brains. We found that the critical concentration for the ion channel formation decreased with increasing the unsaturation degree of the membranes. Moreover, the structural variation of the membranes arising from the Aβ-membrane interaction differed when the membrane composition was different.
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