建立腦部動力學模式探討與阿茲海默症之關聯

Establish Dynamic Model of Human Brain and Discuss the Relation with Alzheimer’s Disease

江哲瑋(ZHE-WEI JIANG)

指導教授 ： 王逢盛

國立中正大學/工學院/化學工程學系/碩士(2016年)

摘要

神經鞘脂類(Sphingolipids)在人體中的分布相當廣泛，其分布在人體的細胞內外及胞器之中，亦可經由飲食中攝取。神經鞘脂類不只是組成細胞膜結構之重要成分，其同時也是訊號傳遞因子，藉由訊號傳遞來調控細胞的存亡。而神經鞘脂類也已經被證實與人體部分疾病如阿茲海默症、癌症等疾病之形成的原因有所關聯，而神經鞘脂類的中間代謝產物神經醯胺(Ceramide)及鞘氨醇-1-磷酸(Sphingosine-1-Phosphate)也分別被證實為抑癌脂質/促凋亡因子及促癌脂質/抗凋亡因子，目前也已經有以這些物質做為癌症治療的藥物[1]。本研究旨在於建立與阿茲海默症(Alzheimer’s Disease)相關之動力學模型[2]，結合文獻及生物資訊來探討系統內之參數出現變動後導致正常情況之系統變成阿茲海默症疾病的系統，由此便可以反向操作來探討如何使在疾病狀況下藉由參數之調控使系統中目標物質如神經醯胺、神經磷脂(Sphingomyelin)等在相關胞器包括溶酶體(Lysosome)、粒線體(Mitochondrion)及內質網(Endoplasmic Reticulum)中的值回到正常狀態，藉此我們可以來找到相關的治療目標及治療方法。

關鍵字

神經鞘脂 ； 神經醯胺 ； 鞘氨醇-1-磷酸 ； 動力學模型

並列摘要

Sphingolipids are widely existed in the human body, they distribute in intracellular、extracellular and different organelles , and they can also be taken through diet. Sphingolipids are not only the main structure of the cell membrane but also can control cell’s death or survival via signaling. Sphingolipids have been linked to some human diseases such as Alzheimer’s disease and some kinds of cancer. Its metabolic pathway intermediates ceramide and sphingosine 1- phosphate are known as tumor- suppressor lipid and cancer-promoting lipid respective, but in neuro-degradation disease they are thought as pro-apoptotic molecule and anti-apoptotic molecule respective. In this research we are going to construct dynamic models that are related to Alzheimer’s disease, and then combines with literatures and bio-information to discuss how normal system turns into disease system by adjusting the parameters that are included in the model. By this way then we can try to find out the way to turn the disease condition back to normal condition through manipulating the disease related species like ceramide and sphingosine-1-phosphate. Also the metabolic balance including in lysosome, mitochondrion and endoplasmic reticulum that are important when disease happened. We will also discuss how the parameters manipulations influence the disease related species in those organelles and finally cause the disease to happen. Through this model research we might find some possible therapy targets or therapy methods to cure or delay the progression of Alzheimer’s disease.

並列關鍵字

sphingolipids ； ceramide ； sphingosine 1-phosphate ； dynamic models

參考文獻

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