帕金森氏症（Parkinson’s disease, PD）是一常見慢性中樞神經系統退化性疾病，臨床病徵包含靜止性顫抖、肌肉僵直、行動遲緩、平衡失調等，此病屬於神經細胞凋亡而引發的神經退化性疾病。有研究指出，PD病因發展和內質網壓力以及自噬作用調節異常有關。目前臨床之治療僅能舒緩部分臨床病徵，卻無法根治，且大部分會伴隨嚴重副作用產生，因此，目前找出新穎帕金森氏症治療藥物是極為重要之一課題。本篇研究中，利用PD離體和活體模式針對海洋化合物Sily-1683對於6-OHDA造成之毒性進行探討。離體實驗結果發現，Sily-1683能夠顯著抑制6-OHDA所誘導之人類神經母細胞瘤(SH-SY5Y)細胞凋亡，並且能夠抑制內質網壓力以及提升自噬作用。而在活體實驗結果則發現，Sily-1683可以顯著抑制6-OHDA所引起之斑馬魚運動行為能力下降，同時亦可降低內質網壓力。由此可知，Sily-1683可能是透過調節內質網壓力和自噬作用達到神經保護的效果，具有發展PD藥物之潛力。

Parkinson's disease (PD) is a degenerative disorder of the central nervous system. Symptoms of PD include resting tremor, rigidity, bradykinesia, and posture instability. Motor symptoms of PD result from the neuronal death in the substantia nigra. Previous studies have shown that both of ER stress and autophagy play important roles in the pathogenesis of PD. Up to the present, there is no effective cure for PD, although medications can provide relief from the symptoms. However, drugs used for PD have been reported that they can cause a variety of side effects. Therefore, it’s important to develop new drugs for treatment of PD. In the present study, in vitro and in vivo model of PD were used to determine the effects of marine compound Sily-1683 against 6-OHDA-induced toxicity. In vitro data revealed that Sily-1683 significantly inhibited 6-OHDA-induced apoptosis in SH-SY5Y cells. Also, Sily-1683 could reduce 6-OHDA-induced ER stress, but enhance autophagy induced by 6-OHDA. And in vivo data showed that Sily-1683 could inhibit 6-OHDA-induced deficits in locomotor activity of zebrafish. Besides, Sily-1683 could reduce ER stress induced by 6-OHDA in zebrafish. These findings reveal that marine compound Sily-1683 exerts its neuroprotective effects probably via regulation of ER stress and autophagy and hence have the potential to be used for the treatment of PD.

論文審定書......i
謝誌......ii
中文摘要......iii
Abstract......iv
目錄......v
圖目錄......vi
表目錄......vii
第一章、前言......1
第二章、實驗材料與方法......25
第三章、實驗結果......39
第四章、討論......70
參考文獻......81

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