近期研究表示磷酸化的Tau蛋白會堆積在細胞質當中並且以插入的方式崁入粒線體的外膜，因而導致粒線體膜電位增加而受損(Hu et al., 2016)。
PINK1/Parkin為主要調節粒線體自噬作用，將受損的粒線體標記並且清除，在此機制當中Parkin為PINK1下游也可經由over-express Parkin來拯救PINK1的缺失(Costa, Loh, & Martins, 2013)。Tau蛋白不正常的堆積以及ParkinT240R mutant皆與帕金森氏症有關。在這裡我們用UAS/GAL4 系統，表現Tau對於Parkin以及ParkinT240R之間在果蠅多巴胺神經元內的相互作用。在我們實驗中，發現同時表現Tau和Parkin以及Tau和ParkinT240R mutant能使單獨表現Tau的果蠅壽命延長，爬行能力也有所改善。不僅如此，磷酸化的Tau也因此減少。另外我們利用UAS-MitoTimer來標記受損粒線體，用於研究受損粒線體在多巴胺神經元內堆積的情形，我們發現Tau和Parkin以及Tau和ParkinT240R mutant 能夠減少受損粒線體堆積在軸突當中，並且我們發現表現Tau在第一周時受損粒線體堆積情形相似於control 組第四周時受損堆積情形。總而言之，我們的研究了解Tau蛋白對於Parkin以及ParkinT240R mutant之間在tyrosine hydroxylase neurons、壽命測試、行為實驗以及粒線體中有許多相互影響的可能性。

Recent studies have shown that phosphorylated tau protein accumulates in the cytoplasm and inserts into the outer membrane of the mitochondria. As a result, the mitochondrial membrane potential increases and is impairs. PINK1/Parkin- mediated mitophagy selectively eliminates damaged mitochondria(Hu et al., 2016). Parkin is the downstream of PINK1 and overexpression of Parkin can rescue PINK1 dysfunction(Costa et al., 2013). Abnormal accumulation of Tau protein and ParkinT240R mutant are associated with Parkinson's disease. In this study, we used UAS/GAL4 system to study the interaction between human wild-type Tau and Parkin in Drosophila dopaminergic neurons. In our study, we found that co-expressing human wild- type Tau and Parkin could prolong the lifespan, improved the locomotion ability and reduced the phosphorylated tau. In addition, we used UAS-MitoTimer to label damaged mitochondria to study the accumulation of damaged mitochondria in dopaminergic neurons. We found that co-expression of human wild-type Tau with Parkin or ParkinT240 mutant could reduce the damaged mitochondrial accumulation in axons. Moreover, we found that the phenotypes of over-expressing human wild-type Tau accumulated damaged mitochondria in axons during aging at 1 week(arrow area) were similar to the control group aging at 4 weeks. In summary, our study shows that wild-type or mutant Parkin and human wild-type Tau have functional interaction in tyrosine hydroxylase neurons, climbing assay, life span and mitochondria.

Content
中文摘要 I
Abstract II
致謝 IV
Introduction 1
Parkinson’s disease (PD) 1
Tau protein 2
PINK1 / Parkin 3
Mitochondria 4
Materials and methods 7
Drosophila culture and strains 7
Lifespan assay 7
Behavioral analysis 7
Immunohistochemistry and confocal images 8
Result 10
Overexpression of Parkin or ParkinT240R would increase the life span under the background of wild-type tau 10
Overexpression of Parkin or ParkinT240R mutant decreased the level of phosphorylated wild-type Tau at 1_week and 4_week. 12
Overexpression of Parkin, ParkinT240R mutant rescued the locomotion defect caused by human wild-type tau at 1_week to 4_week. 13
Overexpression of human wild-type Tau caused damaged mitochondria accumulation in axon. 15
Overexpression of Parkin or ParkinT240R mutant rescued the damaged mitochondrial accumulation phenotype caused by wild-type Tau 16
Discussion 18
Figure 21
Reference 41

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