醫學的進步帶給人類長壽以及死亡率的下降，現代社會已經步入高齡化的發展，逐漸向超齡化社會的危機靠近，老化造成的問題已然成為不可避免的難題，包含論文中探討的阿茲海默症(Alzheimer’s disease，AD)、帕金森氏症(Parkinson’s disease，PD)、亨丁頓舞蹈症(Huntington’s disease)等隨著時間發生的神經退化性疾病。阿茲海默症(以下會簡稱AD)是近年來攀升並具有極大的市場潛力，約有60%-70%癡呆病例的發生原因，而在很久之前AD患者的腦中被找到Tau tangles，造成神經退化性疾病，稱為Tauopathies，認為該機制與AD有關。Tau tangles是Tau異常過度磷酸化並聚集成神經纖維聚合物(NFTs，neurofibrillary tangles)，NFTs的毒性是由於引起神經細胞凋亡所造成的[1]，因此許多科學家開始致力於研究Tau的路徑以及神經退化的關聯，用以調節Tau的信號傳遞而觀察Tau tangles，目的是治療類似機制產生的疾病。
Tau是穩定微管的蛋白質MAPT，主要分布於中樞神經(CNS)，在神經細胞的運輸中具有重要的地位，而我利用v24602這種 Crag RNAi去抑制Crag的表現，導致Rab3 GEF失去功能，藉此了解Tau的表現如何對細胞中的運輸造成影響以及傷害神經的評估。然而經過western blot、immunohistochemistry、行為實驗以及生命週期的大量數據分析，得出的結果是在Cragv24602所造成的損傷下，Tau的表現會在活動能力上得到補償，但是共同作用會產生更嚴重的破壞。

The great development of medicine results in the prolonged human life and the decreasing death rate. The modern society has been an aged society and will entry to the hyper-aged society. The tasks of aging becomes unavoidable and includes those aging-related diseases, such as Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, and so on. Alzheimer’s disease, the cause of 60–70% of cases of dementia, is recently rising and has a great potential market in the future. It was a long time that AD patients was found tau tangles in AD brains causing neurodegeneration and the scientists showed tau pathology was related to AD. Tau tangles are neurofibrillary tangles, called NFTs, assembled by abnormally hypophosphorylated Tau and the toxicity of NFTs is resulted by a neuron cell death signal (Kiran Yanamandra, Najla Kfoury, et al. 2013). Thus they try to figure out the pathway between tau pathology and neurodegeneration, using to regulate signaling transduction of tau for observation to tau tangles. They want to cure those diseases caused by this mechanism for the purpose.
Tau is Microtubule-associated proteins (MAPTs) playing a role for stabilizing axons and vesicle transportation mostly in central nervous system (CNS). Thus we used Crag RNAi, so called CragV24602, to knock down Rab3 GEF for Crag inhibition in order to realize how Tau impacted transportation and damaged dopaminergic neurons with CragV24602. However after the analysis of numerous data from western blot, immunohistochemistry, climbing test, and lifespan, the result was that Tau expression would complement the moving ability during the impact of Cragv24602 and there was a greater damage inducing by the interaction with Crag RNAi and Tau.

致謝…………………………………………………………………………1
Index………………………………………………………………………2
中文摘要…………………………………………………………………3
Abstract………………………………………………………………4
Introduction……………………………………………………6
Supplementary…………………………………………………12
Experimental procedures………………………14
Result……………………………………………………………………18
Discussion…………………………………………………………23
Reference……………………………………………………………26
Figures…………………………………………………………………33

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