阿茲海默症是一種神經退化性疾病，它與tau蛋白磷酸化和β-澱粉粒蛋白的積累有關。但是，它的詳細機制仍然有很多潛在的可能性。自噬作用和tau蛋白磷酸化之間的關係十分有探討的價值，而Vps34基因則是本論文的主要目標基因。Vps34基因被抑制會使得磷酸化的tau蛋白僅僅在大腦周圍累積，不會進入或堆積在神經細胞中，這將導致阿茲海默症發作的時間會延後拉長。除此之外，從免役染色的結果發現，神經細胞內Vps34的表現量在Vps34被抑制後，有顯著下降的趨勢。此外，把Gmrgltau與Vps34被抑制的果蠅交配後產生的後代，他們的壽命只比野生型果蠅減短了1週左右的時間。Vps34會透過線粒體進行該上述的作用，線粒體則會因此無法消耗氧氣，而導致ROS升高。ROS升高的時候，正常情況下會使細胞進行細胞凋亡的步驟，但是由於Vps34表現被抑制，因此細胞凋亡過程將被迫停止在特定位置。基於該結果，可以推測出有一種機制可以保護大腦免受磷酸化tau蛋白的累積。

Alzheimer’s disease is the most common neurodegenerative disease. It relates to the tau protein hyperphosphorylation and β-amyloid accumulation. However, its detailed mechanism still has so many unknown possibilities. One possible protein to the manipulating mechanism of tau and autophagy is Vps34, which is a phosphatidylinositol lipid kinase. The Vps34 gene knockdown can make phosphorylated tau protein merely accumulate around the brain and be unable to attack the brain or even enter neuron cells. The dysfunctional mitochondria would be unable to consume oxygen, and thus, it causes the ROS to rise. Under disease conditions, the ROS rising would make the cell conduct apoptosis. However, when Vps34 is knockdown, we observed that the tau-induced apoptosis process is abnegation. Based on the result, it must be a mechanism protecting the brain from phosphorylated tau protein accumulating when knockdown Vps34. Besides, the life span of the Gmrgltau > Vps34-RNAi Drosophila is only one week shorter than the WT group.

Abstract.............................................................2
摘要.................................................................3
Acknowledge..........................................................4
Introduction.........................................................6
Materials & Methods.................................................12
Results.............................................................15
1.Vps34 knockdown makes Drosophila’s eyes and lives recover to WT...15
2.Vps34 knockdown causes P-tau to be exclusive of the brain.........16
3.Vps34 is more effective on GmrGal4Tau4............................17
Discussion..........................................................19
Figures.............................................................22
Figure 1. Vps34 knockdown potential pathway.........................22
Figure 2. SEM photo of Drosophila’s eyes............................23
Figure 3. Drosophila lifespan.......................................24
Figure 4. Confocal microscopy photo under different genotype........25
Figure 5. The ROS change with Vps34 knockdown.......................27
Figure 6. Possible mechanism of Vps34 knockdown in Drosophila.......29
References..........................................................30

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