LAUSR

Diseases caused by ischemia, including coronary artery disease and stroke, are a leading cause of death worldwide [1]. Restoration of the blood and oxygen supply after restriction also causes tissue damage by activating a number of pathological pathways, such as inflammatory, oxidative stress, and cell death pathways that are mediated by microRNAs and hypoxia-inducible factors [1, 2]. In recent years, thrombolytic and surgical treatments for patients with acute stroke or coronary artery disease have improved and are effective, but currently there is no approved therapy for use after an ischemic stroke [3]. This lack of effective neuroprotective drugs suggests a shortage of proper therapeutic targets for treating ischemia-reperfusion injury. Thus, to uncover new molecules that regulate or mediate ischemia-reperfusion injury, it is necessary to identify novel targets for drug development. The genetic basis of anoxia tolerance is not well understood. Using an anoxiaor hypoxia-tolerant animal model to find new genes involved in such resistance may uncover new pathways for further investigation. One such model is Drosophila, which has been used to investigate the susceptibility or tolerance to anoxia or hypoxia [4, 5]. An estimated 75% of known human disease genes are matched in the genetic code of Drosophila, thus it has frequently been used to model human diseases and these models have been successfully used to study the interactions between disease-related molecules and to screen for disease-modifying drugs and genes [6]. Using a Drosophila model of Alzheimer’s disease [7], we previously conducted a genetic screen for modifiers and identified some genes as novel regulators or mediators of intraneuronal Ab42 accumulation and its associated neural degeneration [8]. Importantly, genetic reduction of a mouse homologue of one of these modifiers found in Drosophila (eighty-five requiring 3 protein in mice and rolling blackout in flies) also suppresses the neurodegeneration in a mouse model of Alzheimer’s disease [9]. Thus, genetic screening for modifiers of disease phenotypes in Drosophila is a reliable means of discovering novel mediators of pathogenesis. Qingqing Du, Nastasia K. H. Lim, Yiling Xia, Wangchao Xu have contributed equally to this work.