Development of diagnostic and therapeutic agents targeting pre- fibrillary tau lesions in Tauopathies.

开发针对 Tau 病中原纤维前 tau 病变的诊断和治疗药物。

• 批准号: 21791158
• 负责人: MARUYAMA Masahiro
• 金额: $ 2.83万
• 依托单位: National Institute of Radiological Sciences
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Young Scientists (B)
• 财政年份: 2009
• 资助国家: 日本
• 起止时间: 2009 至 2010
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-21791158/
• 关键词: タウオパチー; ポジトロン断層撮影; 未線維タウ構造体; ビトロネクチン; 線維性封入体形成機構; 未線維化タウ病変; イメージング

A series of newly developed tau imaging probes applicable to positron emission tomography (PET) exhibited pharmacological properties sufficient for quantitative detection of intraneuronal tau inclusions (TI) formed in tau transgenic mice (tau-Tg). Combined PET and postmortem neuropathological assays of aged tau-Tg indicated that relatively immature tau assemblies in the hippocampus led neurons to toxic death prior to the formation of TI, while abundant accumulation of TI appeared to be associated with gradual neuronal death in the brainstem and spinal cord. This regional difference may be mechanistically linked to interaction of bioactive molecules with tau aggregates, as an adhesion element, vitronectin (Vn), was well colocalized with neuronal tau in the brainstem but not hippocampus. In this consideration, Vn is likely to be involved in conversion of tau polymers between immature neurotoxic and mature nontoxic forms, which would provide insights into etiological and diagnostic-therapeutic approaches to low-order tau assemblies.

一系列新开发的适用于正电子发射断层扫描（PET）的tau成像探针表现出足够的药理学特性，用于定量检测tau转基因小鼠（tau-Tg）中形成的神经元内tau包涵体（TI）。结合PET和尸检神经病理学测定老年tau-Tg表明，海马中相对不成熟的tau组件导致神经元毒性死亡之前，TI的形成，而丰富的积累TI似乎与逐渐的神经元死亡在脑干和脊髓。这种区域差异可能在机械上与生物活性分子与tau聚集体的相互作用有关，因为粘附元件玻连蛋白（Vn）与脑干中的神经元tau很好地共定位，而不是海马体。在这种情况下，Vn可能参与tau聚合物在未成熟神经毒性和成熟无毒形式之间的转化，这将为低阶tau组装的病因学和诊断-治疗方法提供见解。

项目成果

In-vivo optical and PET detections of fibrillar tau lesions in a mouse model of tauopathies

小鼠 tau 病模型中纤维状 tau 病变的体内光学和 PET 检测

• 发表时间: 2009
• 作者: Maruyama M;et al.;Masahiro Maruyama
• 通讯作者: Masahiro Maruyama

In-vivo optical and PET detections of fibrillar tau lesions in a mouse model of tauopathies.

tau 蛋白病小鼠模型中纤维状 tau 蛋白病变的体内光学和 PET 检测。

• 发表时间: 2009
• 作者: Maruyama M;et al.
• 通讯作者: et al.

タウ封入体を標的としたタウオパチー診断薬の開発

针对tau包涵体的tau蛋白病诊断剂的开发

• 发表时间: 2009
• 作者: Higuchi M;Maeda J;Ji B;Maruyama M;Okauchi T;Tokunaga M;Ono M;Suhara T.;丸山将浩
• 通讯作者: 丸山将浩