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  会員専用

• ホーム
• 49巻11号
• 臨床神経, 49：910−912, 2009
• 49巻11号目次

第50回日本神経学会総会

＜シンポジウム9―2＞ポリグルタミン病への分子生物学的アプローチショウジョウバエをもちいたポリグルタミン病へのアプローチ

倉永　英里奈^1）2）, 殿城　亜矢子^1）2）, 三浦　正幸^1）2）

^1）東京大学大学院薬学系研究科遺伝学教室〔〒113-0033　東京都文京区本郷7-3-1〕
^2）CREST, JST

The intracellular accumulation of unfolded or misfolded proteins is believed to contribute to aging and age-related neurodegenerative diseases. However, the links between age-dependent proteotoxicity and cellular protein degradation systems remain poorly understood. Here, we show that 26S proteasome activity and abundance attenuate with age, which is associated with the impaired assembly of the 26S proteasome with the 19S regulatory particle (RP) and the 20S proteasome. In a genetic gain-of-function screen using Drosophila, we characterized Rpn11, which encodes a subunit of the 19S RP, as a suppressor of expanded polyglutamine-induced progressive neurodegeneration. Rpn11 overexpression suppressed the age-related reduction of the 26S proteasome activity, resulting in the extension of flies' life spans with suppression of the age-dependent accumulation of ubiquitinated proteins. On the other hand, the loss of function of Rpn11 caused an early onset of reduced 26S proteasome activity and a premature age-dependent accumulation of ubiquitinated proteins. It also caused a shorter life span and an enhanced neurodegenerative phenotype. Our results suggest that maintaining the 26S proteasome with age could extend the life span and suppress the age-related progression of polyglutamine diseases.
Full Text of this Article in Japanese PDF (458K)

(臨床神経, 49：910−912, 2009)
key words：遺伝学的スクリーニング, ユビキチン―プロテアソーム経路, ショウジョウバエ

（受付日：2009年5月22日）