Faculty of Science, Toho University, Funabashi, Japan.
Tokyo Metropolitan Institute of Medical Science, Tokyo, Japan.
PLoS One. 2018 Sep 18;13(9):e0204048. doi: 10.1371/journal.pone.0204048. eCollection 2018.
APP (amyloid precursor protein), the causative molecule of Alzheimer's disease, is synthesized in neuronal cell bodies and subsequently transported to synapses. We previously showed that the yata gene is required for the synaptic transport of the APP orthologue in Drosophila melanogaster. In this study, we examined the effect of a reduction in yata expression in the Drosophila Alzheimer's disease model, in which expression of human mutant APP was induced. The synaptic localization of APP and other synaptic proteins was differentially inhibited by yata knockdown and null mutation. Expression of APP resulted in abnormal synaptic morphology and the premature death of animals. These phenotypes were partially but significantly rescued by yata knockdown, whereas yata knockdown itself caused no abnormality. Moreover, we observed that synaptic transmission accuracy was impaired in our model, and this phenotype was improved by yata knockdown. Thus, our data suggested that the phenotypes caused by APP can be partially prevented by inhibition of the synaptic localization of a subset of synaptic proteins including APP.
淀粉样前体蛋白（APP）是阿尔茨海默病的致病分子，在神经元胞体中合成，然后运输到突触。我们之前的研究表明，yata 基因是果蝇 APP 同源物突触运输所必需的。在这项研究中，我们在果蝇阿尔茨海默病模型中研究了 yata 表达减少的影响，该模型诱导表达人突变 APP。yata 敲低和缺失突变对 APP 和其他突触蛋白的突触定位有不同的抑制作用。APP 的表达导致了异常的突触形态和动物的过早死亡。yata 敲低部分但显著地挽救了这些表型，而 yata 敲低本身并没有引起异常。此外，我们观察到我们的模型中的突触传递准确性受损，而 yata 敲低可以改善这种表型。因此，我们的数据表明，通过抑制包括 APP 在内的一部分突触蛋白的突触定位，可以部分预防 APP 引起的表型。
