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

Aging Cell

Ching-Tzu Wang¹  Yi-Chun Chen¹  Yi-Yun Wang¹  Ming-Hao Huang¹  Tzu-Li Yen¹  Hsun Li³  Cyong-Jhih Liang¹  Tzu-Kang Sang¹  Shih-Ci Ciou¹  Chiou-Hwa Yuh⁵  Chao-Yung Wang²  Theodore J. Brummel⁴ 

[1] Institute of Biotechnology, National Tsing Hua University, Hsinchu 30013, Taiwan, R.O.C.;Second Section of Cardiology, Department of Internal Medicine, Chang Gung Memorial Hospital at Linkou, Chang Gung University College of Medicine, Taoyuan, Taiwan, R.O.C.;Department of Life Science, National Tsing Hua University, Hsinchu 30013, Taiwan, R.O.C.;Department of Biology, Long Island University, Brookville, NY 11548, USA;Institute of Molecular and Genomic Medicine, National Health Research Institutes, Zhunan Town, Miaoli County 350, Taiwan, R.O.C.

关键词: ribose‐5‐phosphate isomerase;    pentose phosphate pathway;    neuron;    oxidative stress;    longevity;    polyglutamine toxicity;    Drosophila;   

DOI  :  10.1111/j.1474-9726.2011.00762.x

来源: Wiley

【 摘 要 】

Summary

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 Huntington’s 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.

【 授权许可】

Unknown   
© 2011 The Authors. Aging Cell © 2011 Blackwell Publishing Ltd/Anatomical Society of Great Britain and Ireland