Identified the causative gene for EAOH end elucidation the molecular mechanisms of neurodegeneration in EAOH

我们之前已经确定了早发性共济失调伴眼运动失用症和低白蛋白血症（EAOH）的致病基因，这是一种常染色体隐性神经退行性疾病。我们将致病基因命名为“aprataxin”。本研究旨在阐明EAOH神经退行性变的分子机制，并进一步建立该疾病的治疗策略。在之前的研究中，我们发现了aprataxin mRNA有两种主要的亚型，其中我们证明了长形aprataxin是其生理功能所必需的成分。此外，基于酵母双杂交实验和纳米共沉淀实验，我们发现aprataxin与XRCC1 （x射线修复交叉互补组1）相互作用，提出了aprataxin在单链DNA断裂修复（SSBR）中具有生理功能的可能性。体外重建实验表明，阿普拉西辛含有5'-磷酸酶和3'-磷酸酶活性。综上所述，这些发现表明阿普拉辛是参与SSBR的分子的新成员。

We have previously identified the causative gene for early-onset ataxia with ocular motor apraxia and hypoalbuminemia (EAOH), an autosomal recessive neurodegenerative disease. We named the causative gene "aprataxin". This study was aimed to elucidate the molecular mechanisms of neurodegeneration in EAOH and, furthermore, to establish the therapeutic strategies for this diseases. In previous studies we showed that there are two major isoforms of aprataxin mRNA, of which we demonstrated that long form aprataxin is the component essential for its physiological function. Furthermore, we identified that aprataxin interacts with XRCC1 (X-ray repair cross complementing group 1) based on yeast two hybrid assay as well as im nuno coprecipitation experiments, raising the possibility that aprataxin has a physiological function in single strand DNA break repair (SSBR). In vitro reconstitution experiments of SSBR demonstrated that aprataxin contains 5'-phophatase as well as 3'-phophatase activities.Taken together these findings suggest that aprataxin is a new member of molecules involved in SSBR.