title: Reduced neuronal expression of ribose-5-phosphate isomerase enhances tolerance to oxidative stress, extends lifespan, and attenuates polyglutamine toxicity in Drosophila.
abstract: 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.
authors: Institute of Biotechnology, National Tsing Hua University, Hsinchu, Taiwan, ROC.
authors: Ching-Tzu
authors: CT
authors: Wang
authors: Yi-Chun
authors: YC
authors: Chen
authors: Yi-Yun
authors: YY
authors: Wang
authors: Ming-Hao
authors: MH
authors: Huang
authors: Tzu-Li
authors: TL
authors: Yen
authors: Hsun
authors: H
authors: Li
authors: Cyong-Jhih
authors: CJ
authors: Liang
authors: Tzu-Kang
authors: TK
authors: Sang
authors: Shih-Ci
authors: SC
authors: Ciou
authors: Chiou-Hwa
authors: CH
authors: Yuh
authors: Chao-Yung
authors: CY
authors: Wang
authors: Theodore J
authors: TJ
authors: Brummel
authors: Horng-Dar
authors: HD
authors: Wang
mesh_terms: D000375:Aging / Q000235:genetics / Q000378:metabolism*; D019747:Aldose-Ketose Isomerases / Q000172:deficiency / Q000235:genetics*; D000818:Animals; D004195:Disease Models, Animal; D029721:Drosophila Proteins / Q000172:deficiency / Q000235:genetics*; D004331:Drosophila melanogaster; D055785:Gene Knockdown Techniques; D006801:Humans; D006816:Huntington Disease / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D008136:Longevity; D008297:Male; D009249:NADP / Q000378:metabolism; D009474:Neurons / Q000378:metabolism / Q000473:pathology; D018384:Oxidative Stress; D010427:Pentose Phosphate Pathway / Q000235:genetics*; D010455:Peptides / Q000235:genetics / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000235:genetics; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D029721:Drosophila Proteins; D010455:Peptides; D034741:RNA, Small Interfering; D017382:Reactive Oxygen Species; C097188:polyglutamine; D009249:NADP; D019747:Aldose-Ketose Isomerases; C022548:ribosephosphate isomerase