Reduced neuronal expression of ribose-5-phosphate isomerase enhances tolerance to oxidative stress, extends lifespan, and attenuates polyglutamine toxicity in Drosophila

被引：28

作者：

Wang, Ching-Tzu ^{[1
]}

Chen, Yi-Chun ^{[1
]}

Wang, Yi-Yun ^{[1
]}

Huang, Ming-Hao ^{[1
]}

Yen, Tzu-Li ^{[1
]}

Li, Hsun ^{[2
]}

Liang, Cyong-Jhih ^{[1
]}

Sang, Tzu-Kang ^{[1
,2
]}

Ciou, Shih-Ci ^{[1
]}

Yuh, Chiou-Hwa ^{[3
]}

Wang, Chao-Yung ^{[4
]}

Brummel, Theodore J. ^{[5
]}

Wang, Horng-Dar ^{[1
,2
]}

机构：

[1] Natl Tsing Hua Univ, Inst Biotechnol, Hsinchu 30013, Taiwan

[2] Natl Tsing Hua Univ, Dept Life Sci, Hsinchu 30013, Taiwan

[3] Natl Hlth Res Inst, Inst Mol & Genom Med, Zhunan Town 350, Miaoli County, Taiwan

[4] Chang Gung Univ, Chang Gung Mem Hosp Linkou, Coll Med, Sect Cardiol 2,Dept Internal Med, Tao Yuan, Taiwan

[5] Long Isl Univ, Dept Biol, Brookville, NY 11548 USA

来源：

AGING CELL | 2012年 / 11卷 / 01期

基金：

美国国家卫生研究院;

关键词：

ribose-5-phosphate isomerase; pentose phosphate pathway; neuron; oxidative stress; longevity; polyglutamine toxicity; Drosophila; PENTOSE-PHOSPHATE PATHWAY; GLUCOSE-6-PHOSPHATE-DEHYDROGENASE ACTIVITY; ADULT DROSOPHILA; NERVOUS-SYSTEM; MELANOGASTER; LONGEVITY; RESISTANCE; NEURODEGENERATION; OVEREXPRESSION; APOPTOSIS;

D O I：

10.1111/j.1474-9726.2011.00762.x

中图分类号：

Q2 [细胞生物学];

学科分类号：

071013 [干细胞生物学];

摘要：

Aging and age-related diseases can be viewed as the result of the lifelong accumulation of stress insults. The identification of mutant strains and genes that are responsive to stress and can alter longevity profiles provides new therapeutic targets for age-related diseases. Here we reported that a Drosophila strain with reduced expression of ribose-5-phosphate isomerase (rpi), EP2456, exhibits increased resistance to oxidative stress and enhanced lifespan. In addition, the strain also displays higher levels of NADPH. The knockdown of rpi in neurons by double-stranded RNA interference recapitulated the lifespan extension and oxidative stress resistance in Drosophila. This manipulation was also found to ameliorate the effects of genetic manipulations aimed at creating a model for studying Huntingtons disease by overexpression of polyglutamine in the eye, suggesting that modulating rpi levels could serve as a treatment for normal aging as well as for polyglutamine neurotoxicity.

引用

页码：93 / 103

页数：11

共 46 条

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