Muffat Julien, Walker David W, Benzer Seymour
Division of Biology, California Institute of Technology, Pasadena, CA 91125, USA.
Proc Natl Acad Sci U S A. 2008 May 13;105(19):7088-93. doi: 10.1073/pnas.0800896105. Epub 2008 May 5.
Apolipoprotein D (ApoD) expression increases in several neurological disorders and in spinal cord injury. We provide a report of a physiological role for human ApoD (hApoD): Flies overexpressing hApoD are long-lived and protected against stress conditions associated with aging and neurodegeneration, including hyperoxia, dietary paraquat, and heat stress. We show that the fly ortholog, Glial Lazarillo, is strongly up-regulated in response to these extrinsic stresses and also can protect in vitro-cultured cells in situations modeling Alzheimer's disease (AD) and Parkinson's disease (PD). In adult flies, hApoD overexpression reduces age-associated lipid peroxide accumulation, suggesting a proximal mechanism of action. Similar data obtained in the mouse [Ganfornina, M.D., et al., (2008) Apolipoprotein D is involved in the mechanisms regulating protection from oxidative stress. Aging Cell 10.1111/j.1474-9726.2008.00395.] as well as in plants (Charron et al., personal communication) suggest that ApoD and its orthologs play an evolutionarily conserved role in response to stress, possibly managing or preventing lipid peroxidation.
载脂蛋白D（ApoD）在多种神经系统疾病和脊髓损伤中表达增加。我们报告了人类ApoD（hApoD）的生理作用：过表达hApoD的果蝇寿命延长，并能抵御与衰老和神经退行性变相关的应激条件，包括高氧、饮食百草枯和热应激。我们发现果蝇直系同源物胶质拉扎里洛在这些外在应激反应中强烈上调，并且在模拟阿尔茨海默病（AD）和帕金森病（PD）的情况下也能保护体外培养的细胞。在成年果蝇中，hApoD过表达减少了与年龄相关的脂质过氧化物积累，提示了一种近端作用机制。在小鼠[Ganfornina, M.D., 等人，(2008) 载脂蛋白D参与调节抗氧化应激的机制。《衰老细胞》10.1111/j.1474 - 9726.2008.00395.]以及植物（Charron等人，个人交流）中获得的类似数据表明，ApoD及其直系同源物在应激反应中发挥进化上保守的作用，可能管理或预防脂质过氧化。
