Bedeutung funktioneller Domänen von Ataxin-3 beim Transport und Abbau fehlgefalteter Proteine

ataxin-3 功能域在错误折叠蛋白转运和降解中的重要性

• 批准号: 48410914
• 负责人: Professor Dr. Ullrich Wüllner
• 金额: --
• 依托单位: Klinik und Poliklinik für Neurologie
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2007
• 资助国家: 德国
• 起止时间: 2006-12-31 至 2011-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/48410914?language=en
• 关键词: Bedeutung; funktioneller; Dom; nen; von

The immune system is involved in Alzheimer (AD) and Parkinson disease (PD) by the development of a prominent neuroinflammation and a specific activation of the immune system leads to reduced pathogenesis in mouse models for both diseases. Additionally our laboratory has shown recently that human regulatory T cells (Treg) increase in number with age and are more active in AD and PD patients. These changes in Treg support the hypothesis that the course of either disease may be influenced by autoimmune mechanisms, which could be influenced by Treg function. To validate this hypothesis and to elucidate which immune cells contribute to immunotherapeutic approaches, we have generated several mouse lines in mouse models for AD and PD related pathologies, which are deficient for either Treg or immune cells affected by Treg. Analyzing these mouse lines under normal and immune therapeutic conditions with biochemical and neuropathological methods will identify immune cell types involved in progression or prevention of disease related pathology. Additionally, the treatment of immune deficient mouse lines may reveal further immunotherapeutic effector mechanisms usually masked by more dominant mechanisms, which may be used for the development of new therapeutic strategies.

免疫系统通过显着的神经炎症的发展参与阿尔茨海默病（AD）和帕金森病（PD），并且免疫系统的特异性激活导致这两种疾病的小鼠模型的发病机制减少。此外，我们的实验室最近表明，人类调节性 T 细胞 (Treg) 的数量随着年龄的增长而增加，并且在 AD 和 PD 患者中更加活跃。 Treg 的这些变化支持这样的假设：这两种疾病的病程可能受到自身免疫机制的影响，而自身免疫机制又可能受到 Treg 功能的影响。为了验证这一假设并阐明哪些免疫细胞有助于免疫治疗方法，我们在 AD 和 PD 相关病理的小鼠模型中生成了多个小鼠品系，这些小鼠品系缺乏 Treg 或受 Treg 影响的免疫细胞。使用生化和神经病理学方法在正常和免疫治疗条件下分析这些小鼠系将识别参与疾病相关病理进展或预防的免疫细胞类型。此外，免疫缺陷小鼠系的治疗可能进一步揭示通常被更多主导机制掩盖的免疫治疗效应机制，这可用于开发新的治疗策略。