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

在阿尔茨海默病（AD）和帕金森病（PD）的小鼠模型中，免疫系统参与了一种突出的神经炎症的发展，免疫系统的特异性激活导致两种疾病的发病机制减少。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，在AD和PD患者中更活跃。Treg的这些变化支持了一种假设，即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产生了几种小鼠系，这些小鼠系缺乏Treg或受Treg影响的免疫细胞。用生化和神经病理学方法分析正常和免疫治疗条件下的这些小鼠系，将确定参与疾病相关病理进展或预防的免疫细胞类型。此外，对免疫缺陷小鼠品系的治疗可能揭示更多的免疫治疗效应机制，这些机制通常被更主要的机制所掩盖，这可能用于开发新的治疗策略。

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.