第50回日本神経学会総会
＜シンポジウム7―2＞パーキンソン病の病因・診断・治療研究の進歩
孤発性パーキンソン病の病因：リスク遺伝子と環境因子
高橋 良輔, 川又 純, 竹内 啓喜
京都大学大学院医学研究科・臨床神経学〔〒606-8507 京都市左京区聖護院川原町54〕
Parkinson's disease (PD) is the most common neurodegenerative disease after Alzheimer's disease. Although the pathogenetic mechanisms underlying PD is largely unknowm, it is widely believed that multiple genetic as well as environmental factors play critical roles in the development of PD. Alpha synuclein (a-SYN) and the disturbance of a-SYN metabolism seems to play the most important role in PD pathogenesis. a-SYN, the gene causative in PARK1, is the major component of Lewy bodies. Gene duplication or triplication of a-SYN leads to autosomal dominant form of familial PD, suggesting that disturbance of a-SYN may represent the etiology of sporadic PD. GBA and LRRK, the genes responsible for Gaucher disease and PARK8, respetively, are also likely to affect the development of PD. Studies of PD brains suggest that mitochondrial impairment and oxidative stress may contribute to the pathogenesis of sporadic PD. Mitochondrial complex I inhibitors, such as MPTP and rotenone, induce selective dopaminergic neuronal death, suggesting that chemicals may constitute risk factors of sporadic PD. Not only continuous infusion, but oral intake of rotenone is effective to establish animal models of PD. Further studies will reveal genetic or environmental risk factors, that are the good targets for prevention and therapy of PD.
Full Text of this Article in Japanese PDF (267K)
(臨床神経, 49：885−887, 2009)
key words：α-シヌクレイン, 26Sプロテアソーム, ゴーシェ病, MPTP, ロテノン
（受付日：2009年5月22日）
