LRRK2(Leucine-repeat-kinase 2)是一種多結構功能的蛋白質，分子量為285 kD。已知有多種不同位置的點突變被發現，在遺傳性巴金森病家族(familial parkinsonism)中是最普遍被發現的突變基因。然而；此蛋白質在生物中的功能仍不清處。在本研究中我們利用果蠅為實驗生物，表現LRRK2在神經細胞中可以增加果蠅壽命及增加對壓力的抗性。例如在果蠅全身神經表現LRRK2，可以抵抗百草枯(paraquat)及魚藤酮(rotenone)所造成的氧化壓力。利用果蠅眼睛專一的driver共同表現長鏈聚麩醯胺(polyglutamine)和LRRK2可以拯救41Q所造成的眼睛退化，但是無法防止63Q 及108 Q所造成的眼睛退化。此外；我們用了3個細胞凋亡基因grim, reaper及hid去測試LRRK2對凋亡基因的拯救作用，我們發現LRRK2可以拯救grim所導致的果蠅眼睛退化，但是無法拯救hid 及reaper所導致的眼睛退化。在果蠅全身神經表現LRRK2可以增加壽命及抗氧化壓力，為了測試果蠅對對氧化壓力的反應區位，我們用了Ddc-Gal4(dopa-decarboxylase)driver和TH(dopaminergic)及TPH(sertoningeric)的Gal4 driver表現LRRK2。和原先預期的相反；TH的神經並不能表現抗氧化壓力，而TPH 表現的神經在較低濃度(5mM)的百草枯測試下對果蠅具有保護作用 。本研究總結下列結論:表現LRRK2基因可以增加果蠅壽命及抗氧化壓力；並對41Q造成的果蠅眼退化有抑制作用以及降低grim 對果蠅眼睛造成的退化及變小有恢復的效果。

Leucinerichrepeat kinase 2(LRRK2) is a multifunctional domain protein, which molecular weight is 285kD.There have been identified that many mutation cause familial Parkinson disease.LRRK2 gene mutations are the most common genetic cause of Parkinson’s disease. However, little is known about the biological function of LRRK2 gene. In m ystudy, I use Drosophila as an animal model; overexpression of LRRK2 can increase Drosophila lifespan and resistance to oxidative stress. For example expression by pan neuronal driver Elav can extend lifespan and oxidative stress caused by paraquat and rotenone. Using GMR specific Gal4 driver to expression PolyQ and LRRK2 simultaneously can ameliorate 41Q induce eye degeneration, but not for 63Q and 108Q longer PolyQ induce toxicity. Moreover, I use three apoptosis related gene to examine the rescue efficiency by expression LRRK2 gene. I found that LRRK2 can reverse grim caused eye degeneration and down-size fly eyes, but there is little effect on hid or reaper induced eye abnormality. Ubiquitous expression of LRRK2 extends Drosophila lifespan and increase oxidative stress resistance. Toexamine which tissue is responsible for resistance to oxidative stress, we use Ddc(dopa-decarboxylase) Gal4 driver and its subset neuron drivers TH(dopaminergic) and TPH(serotoninergic)neurons, unlike our expectations, there is no protection on TH drive LRRK2 neurons ;however there is partially protection at lower concentration of paraquat on TPH neurons. To summarize my research, there is lifespan extension in Drosophila and oxidative stress by overexpression LRRK2 gene, and protection from 41Q induced eye degeneration. Finally expressions of LRRK2 show reduce the ability to grim cause down size of fly eyes and eye degeneration.

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