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

肌张力障碍分子发病机制的转化研究及其新的治疗干预措施

• 批准号: 21390269
• 负责人: KAJI Ryuji
• 金额: $ 11.15万
• 依托单位: The University of Tokushima
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2009
• 资助国家: 日本
• 起止时间: 2009 至 2011
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-21390269/
• 关键词: 臨床神経生理学; 神経科学; 脳神経疾患; 遺伝子; ゲノム; 国際協力; ジストニア; DYT3; PET

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.

肌张力障碍的发病率约为帕金森症的四分之一，并且并不是一种罕见的疾病。如果病情严重，患者将无法卧床不起。我们首次发现引起遗传性肌张力障碍DYT3的基因（TAF-1），目前日本已有报道。因此，寻找其发病机制和治疗方法具有重要意义。我们之前发现 DYT3 尸检大脑中基底神经节纹状体内的纹状体内神经元选择性丢失。在这项研究中，我们发现 NTAF-1（TAF-1 的一种神经元特异性亚型）主要位于纹状体中，它将分子发病机制与病理和临床结果联系起来。我们还报道了唑吡坦治疗一般肌张力障碍的临床用途。我们开发了 DYT3 肌张力障碍的筛查测试，并尝试对 DYT3 患者进行手术治疗，取得了良好的效果。

项目成果

Comparison of effects of botulinum toxin subtype A1 and A2 using twitch tension assay and rat grip strength test

• DOI: 10.1016/j.toxicon.2010.10.009
• 发表时间: 2011-01-01
• 期刊: TOXICON
• 影响因子: 2.8
• 作者: Torii, Yasushi;Kiyota, Naotoshi;Ginnaga, Akihiro
• 通讯作者: Ginnaga, Akihiro

CELL TYPE-SPECIFIC LOCALIZATION OF OPTINEURIN IN THE STRIATAL NEURONS OF MICE: IMPLICATIONS FOR NEURONAL VULNERABILITY IN HUNTINGTON'S DISEASE

• DOI: 10.1016/j.neuroscience.2011.11.059
• 发表时间: 2012-01-27
• 期刊: NEUROSCIENCE
• 影响因子: 3.3
• 作者: Okita, S.;Morigaki, R.;Goto, S.
• 通讯作者: Goto, S.

Olfactory type G-protein alpha subunit in striosome-matrix dopamine systems in adult mice.

成年小鼠纹状体基质多巴胺系统中的嗅觉型 G 蛋白 α 亚基。

• 发表时间: 2010
• 期刊: Neuroscience
• 影响因子: 3.3
• 作者: Sako W;Morigaki R;Nagahiro S;Kaji R;Goto S.
• 通讯作者: Goto S.

Long-term suppression of Meige syndrome after pallidal stimulation : a 10-year follow-up study

苍白球刺激后梅格综合征的长期抑制：一项 10 年随访研究

• 发表时间: 2010
• 期刊: Mov Disord
• 作者: Inoue N;Nagahiro S;Kaji R;Goto S.
• 通讯作者: Goto S.

Japanese study experience sharing Upper limb study(BTX108509)

日本学习经验分享 上肢学习(BTX108509)

• 发表时间: 2010
• 作者: Umeda T;Mori H;Zheng H;Tomiyama T.;Kaji R
• 通讯作者: Kaji R