Translational study of molecular pathogenesis on dystonia and developing its novel therapeutic interventions

肌张力障碍的发生率约为帕金森症的四分之一，并不是一种罕见的疾病。如果晚期患者卧床不起，它会使患者丧失工作能力。我们首次发现了导致遗传性肌张力障碍DYT3的基因(TAF-1)，目前在日本有报道。因此，寻找其发病机制和治疗方法具有重要意义。我们先前在DYT3尸检脑中发现基底节纹状体纹状体神经元的选择性丢失。在这项研究中，我们发现TAF-1的神经元特异性亚型NTAF-1主要定位于纹状体，其分子发病机制与病理和临床研究相联系。我们还报道了唑吡坦治疗肌张力障碍的临床应用。我们开发了一种DYT3肌张力障碍的筛查测试，并尝试对一名DYT3患者进行手术治疗，结果非常好。

Dystonia is about one fourth as frequent as parkinsonism, and is not a rare disorder. It incapacitates sufferers to be bed-ridden if advanced. We for the first time found the gene(TAF-1) causing a hereditary dystonia DYT3, which is now being reported in Japan. It is therefore important to search for its pathogenesis and therapy. We previously found selective loss of neurons in striosome in the striatum of the basal ganglia in DYT3 autopsied brains. In this research, we found that NTAF-1, a neuron-specific isoform of TAF-1 is mainly localized in the striosome, which links the molecular pathogenesis with pathological and clinical findings.We also reported clinical usefulness of zolpidem for treating dystonia in general. We developed a screening test for DYT3 dystonia, and tried a surgical treatment on a DYT3 patient with excellent outcomes.