Abstract
Abstract Parkinson’s disease (PD) is one of the most common age-dependent neurodegenerative diseases. It is characterized by the movement dysfunctions. These abnormalities may result from the progressive loss of dopamine neurons in the brain. The molecular pathogenesis of tau associated Parkinson’s disease is still unclear. In this study, we focused on two PD genes, LRRK2 and MAPT. We used GAL4/UAS system to express these two human PD genes in the brains of Drosophila melanogaster.Drosophila since this animal model has the advantage of genetic manipulation and the short lifespan. And there are similarities in the nerve system between human and fly. We expressed these PD genes in different neurotransmitter systems in fly brain. And we analyzed their influences in the varied types of neurons. We found that monogenic expression of MAPT produced progressive dopaminergic neuronal degeneration and tau containing tangles which recaptured the key pathogenesis seen in the brains of PD patients. Therefore, it is possible that we could investigate the molecular mechanism of how tau caused PD in fly brain. We also found that similar groups in different neuronal system were affected by tau protein expression. It implicated that the neurons suffer degeneration might related to their function. And we introduced the MARCM method into our experiment thus we might study these PD genes on single-neuron level in future. 摘要 帕金森氏症 (Parkinson’s disease) 是一種常見的神經退化性疾病，多數發生在較老的年齡層中，其外在病徵主要為在運動能力障礙。這些病徵可能是由腦內黑質區域的多巴胺神經細胞凋亡所導致。帕金森氏症確切的致病機制尚未完全明瞭，外在因素如腦部創傷及某些毒素或是經由家族的遺傳皆有可能會引起帕金森氏症的產生。目前已經有許多和帕金森氏症相關的基因被發現，這些基因以及其突變可能會影響得到帕金森氏症的機率。我們的研究主要著重在兩個與帕金森氏症相關的基因上，其為LRRK2和MAPT(tau)。我們利用了GAL4/UAS方法來將人類LRRK2和tau蛋白質表現在果蠅的腦中。果蠅具有方便於基因操控及較短的生命週期等優點，且果蠅的腦部和人類有許多相似之處，例如兩者會利用共同的神經傳遞物質。依照所用的神經傳遞物質，果蠅腦部神經被區分為不同群組。我們使LRRK2和MAPT基因表現這些不同的群組之中，並觀察這些帕金森氏症相關的基因會對神經細胞造成何種影響。在我們的結果中可看到，MAPT基因的表現會重現類似帕金森氏症的病癥，造成果蠅腦內多巴胺神經細胞的凋亡。因此，我們將可以在果蠅腦內研究更多帕金森氏症基因的功能及交互作用。此外，我們也採用了MARCM這個方法，以期未來能夠在單一神經細胞的規模中，觀察帕金森氏症相關基因在果蠅腦內造成的影響。