由基因研究的角度剖析巴金森氏病之致病機轉

巴金森氏病是第二常見的神經退化性疾病。其病理上最主要的特徵為在黑質中的多巴胺神經元的凋零死亡，以及殘留的神經元細胞質中有不正常的包涵體-路易體，導致下游的紋狀體接收不到足夠的多巴胺，因而產生種種的臨床症狀。雖然目前給予病患左多巴的補充治療可以改善病患動作方面的症狀，但是卻無法遏止此疾病隨年齡的惡化，目前仍缺乏根本的治療。導致黑質中多巴胺神經細胞提早死亡的致病機轉目前仍晦暗未明，環境與遺傳因素皆被認為是導致巴金森氏病病患腦中多巴胺神經退化的重要原因之一。截至目前為止，已有15 個巴金森氏病易感基因座與11 個致病基因的突變被證實是引起少數遺傳性巴金森氏病的致病基因，這些基因的發現替釐清巴金森氏病的致病機轉開啟了一道曙光。本文將有系統的回顧引起遺傳性巴金森氏病的重要基因的臨床重要性與其在細胞中扮演之功能，在此，我們回顧了有關基因與家族性巴金森病的最新進展與相關的研究。這些概念可以被用來進一步了解巴金森氏病的病理生理機轉，並作為未來開發治療巴金森氏病的治療策略的一個構想平台。

Parkinson's disease (PD) is one of the most common neurodegenerative disorders with hallmarks of loss of dopaminergic neurons in the substantia nigra. The molecular mechanisms underlying neuronal degeneration in PD remain largely unknown. It is known that genetic factors contribute to the pathogenesis of this disease. There are 5-10 % of PD patients with clear family history, which show a classical recessive or dominant Mendelian mode of inheritance. During the past decade, identification of 11 causative genes linked to familial forms of PD has shed light on the pathogenesis of PD. Recent evidence demonstrated that these PD causative genes play important roles in cellular functions, such as mitochondrial functions, ubiquitin-proteasomal system and membrane trafficking. Herein, we review recent progress in researches concerning about the genes associated with familial PD. These concepts can be used to further understand disease pathophysiology and serve as a platform to develop therapeutic strategies for PD.