第49回日本神経学会総会
＜シンポジウム8-3＞パーキンソン病の臨床，基礎の最前線
パーキンソン病の病態：分子生物学からわかったこと
武田 篤, 菅野 直人, 長谷川 隆文, 小林 理子, 菊池 昭夫
東北大学大学院医学系研究科神経感覚器病態学講座神経内科学分野〔〒980-8574 仙台市青葉区星陵町1-1〕
To explore pathogenesis of synucleinopathy including Parkinson's disease and multiple system atrophy, we developed cellular model for synucleinopathy. In this experimental model, α-synuclein was overexpressed in SH-SY5Y cells, which were then exposed to mitochondrial toxins. The data thus obtained suggested the followings.
1) By the treatment with rotenone, wild type α-synuclein overexpressing cells demonstrated intracellular aggregations, which shared a number of features with Lewy bodies.
2) The aggregate formation of α-synuclein may be cytoprotective.
3) The catechol-derived quinones are candidate molecules to facilitate the oligomer formation of α-synuclein.
4) The cells overexpressing S129A mutant showed few aggregations. It is suggested that phosphorylation at serine 129 is essential for aggregate formation.
5) In wild-type α-synuclein cells treated with rotenone, unfolded protein response (UPR) markers were induced prior to the induction of mitochondrial disruption and caspase-3 activation.
6) On the other hand, the S129A mutant failed to activate these UPRs. Thus it seems plausible that α-synuclein toxicity is dependent on the phosphorylation at S129.
Full Text of this Article in Japanese PDF (156K)
(臨床神経, 48：984−985, 2008)
key words：シヌクレイノパチー, ERストレス, キノン体, 凝集体
（受付日：2008年5月17日）
