Complement and Inflammation in Pathogenesis of Dementia

描述(改编自应用程序)：AD是一种常见的痴呆症或痴呆 认知能力，这与脑组织退化有关。 这种神经变性的原因正在紧张的调查中，作为一种 为这种虚弱和昂贵的疾病设计治疗方法的关键一步 疾病。在各种测试系统中，纤维β-淀粉样蛋白显示 通过其与神经元的直接相互作用以及通过 它与小胶质细胞的相互作用(S)及其激活小胶质细胞的能力 补充制。多项研究表明，反应性 小胶质细胞、星形胶质细胞和补体系统的蛋白质是相关的 与阿尔茨海默病大脑中的老年斑相吻合，与假设一致 由补体系统激活引发的炎症可能 有助于导致认知丧失的病理的产生 在这种疾病中见过。补体(C)系统是一个强大的效应器 免疫系统的机制。然而，组织损伤可能会导致 这一系统的慢性或不受管制的激活。尽管如此，它也是 越来越明显的是，一些补充成分提供了 在受伤区域发挥保护作用。因此，在这个研究项目中， 将利用新的小鼠模型来检验这一假说 在AD的发病机制中起一定作用。潜在的保护作用 将评估这种疾病中的特定补体成分并 调节这些的蛋白质-蛋白质相互作用的特定假说 将对功能进行测试。将使用有机类型培养系统来 评估特定补体成分的修饰能力 淀粉样蛋白诱导的小胶质细胞激活及其对神经变性的影响。 最后，研究人员将利用唐氏综合症组织进一步 评估补体激活、炎症和 痴呆症。这些研究应该提供可靠的数据，说明 补体激活和炎症事件在AD和其他形式的AD中的作用 痴呆症，可以有针对性地减缓痴呆进展的事件 疾病。因为补体已经牵涉到了许多其他 神经退行性疾病，很可能这些发现将是相关的 对其他疾病也是如此。

DESCRIPTION (Adapted from the application): AD is a common dementia or loss of cognitive abilities, which is linked to degeneration of brain tissue. The cause of this neurodegeneration is under intense investigation, as a critical step toward designing therapies for this debilitating and costly disease. In a variety of test systems, fibrillar beta-amyloid displays neurotoxic properties via its direct interaction with neurons but also via its interaction(s) with microglia and its ability to activate the complement system. Multiple studies have demonstrated that reactive microglia, astrocytes and proteins of the complement system are associated with the senile plaques in AD brain, consistent with the hypothesis that inflammation initiated by the activation of the complement system may contribute to the generation of pathology that leads to the cognitive loss seen in this disease. The complement (C) system is a powerful effector mechanism of the immune system. Tissue damage can result however, from chronic or unregulated activation of this system. Nevertheless, it is also becoming increasingly evident that some complement components provide protective functions in areas of injury. Thus, in this research program novel mouse models will be utilized to test the hypothesis that complement plays a role in the pathogenesis of AD. Potential protective effects of specific complement components in this disorder will be assessed and specific hypotheses of the protein-protein interactions that regulate these functions will be tested. Organotypic culture systems will be used to assess the ability of specific complement components to modify amyloid-induced microglial activation and its effect on neurodegeneration. Finally, the investigators will utilize Down Syndrome tissue to further assess the correlation between complement activation, inflammation and dementia. These studies should provide solid data on the significance of complement activation and inflammatory events in AD and other forms of dementia, events that could be targeted to slow the progression of the disease. Since complement has been implicated in a number of other neurodegenerative diseases, it is likely that the findings will be relevant to other diseases as well.