Pgant4 and Tango1 Mediate Anoxia and Reoxygenation Injury
Pgant4 and Tango1 Mediate Anoxia and Reoxygenation Injury
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DOI：
10.1007/s12264-020-00562-y
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发表时间：
2020-08
影响因子：
5.6
通讯作者：
Qingqing Du;N. Lim;Yiling Xia;Wangchao Xu;Qichao Zhang;LiYao Zhang;Fude Huang;Wenan L. Wang
中科院分区：
文献类型：
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作者：
Qingqing Du;N. Lim;Yiling Xia;Wangchao Xu;Qichao Zhang;LiYao Zhang;Fude Huang;Wenan L. Wang
由缺血引起的疾病，包括冠状动脉疾病和中风，是世界范围内死亡的主要原因。限制后血液和氧气供应的恢复也会通过激活一些病理途径引起组织损伤，如炎症、氧化应激和细胞死亡途径，这些途径是由microrna和缺氧诱导因子介导的[1,2]。近年来，急性脑卒中或冠状动脉疾病患者的溶栓和手术治疗已经得到改善和有效，但目前尚无批准用于缺血性脑卒中后的治疗方法。缺乏有效的神经保护药物提示缺乏适当的治疗靶点来治疗缺血再灌注损伤。因此，为了发现调节或介导缺血再灌注损伤的新分子，有必要确定药物开发的新靶点。耐缺氧的遗传基础尚不清楚。使用耐缺氧或耐缺氧动物模型来寻找参与这种抗性的新基因可能会为进一步研究发现新的途径。果蝇就是这样的一个模型，它被用来研究对缺氧或低氧的易感性或耐受性[4,5]。据估计，75%的已知人类疾病基因在果蝇的遗传密码中是匹配的，因此它经常被用来模拟人类疾病，这些模型已经成功地用于研究疾病相关分子之间的相互作用以及筛选疾病修饰药物和基因[6]。利用阿尔茨海默病的果蝇模型[7]，我们先前进行了基因修饰筛选，并确定了一些基因作为神经元内Ab42积累及其相关神经变性[8]的新调节或介质。重要的是，在果蝇中发现的这些修饰物之一的小鼠同源物的遗传减少（小鼠中85需要3蛋白，果蝇中滚动停电）也抑制了阿尔茨海默病小鼠模型中的神经变性。因此，对果蝇疾病表型的修饰因子进行遗传筛选是发现新的发病介质的可靠手段。
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 anoxia-or 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.