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Analyses of the direct effects of Interleukin-4 signaling in neural stem/progenitor cells in control and Alzheimer's mice

分析白细胞介素 4 信号传导对对照小鼠和阿尔茨海默氏症小鼠神经干细胞/祖细胞的直接影响

基本信息

批准号：
394235181
负责人：
Dr. Caghan Kizil
金额：
--
依托单位：
Standort Dresden
依托单位国家：
德国
项目类别：
Research Grants
财政年份：
2017
资助国家：
德国
起止时间：
2016-12-31 至 2020-12-31
项目状态：
已结题

来源：
https://gepris.dfg.de/gepris/projekt/394235181?language=en
关键词：
Analyses direct effects Interleukin signaling

项目摘要

Alzheimer's disease is the most common form of dementia among elderly individuals; however, there is no cure for this disease yet. Alzheimer's disease is characterized by the chronic loss of neurons and synapses in the cerebral cortex, and by a significant loss of brain mass in a progressive manner. Additionally, the neural stem/progenitor cells that have the capacity to generate more neurons cease to proliferate, and therefore cannot produce more neurons. All of these properties of an Alzheimer brain prevents a successful regeneration of our brains in disease conditions. An important aspect of regenerative therapies for Alzheimer's disease is to design novel and unconventional therapeutic approaches. One particular way might be to mobilize the endogenous neural stem/progenitor cells to enhance their proliferation rate and differentiation capacity. When combined with approaches aiming to increase the survival and integration of neurons into circuitry, elevated levels of newly born neurons might provide a regenerative input in a highly unfavorable neurodegenerative environment. Therefore, it is of utmost importance to understand the behavior of stem cells during neurodegeneration, and how they can be coaxed to produce more neurons.In zebrafish, we have identified an immune-related molecules, IL4, which increases the proliferation of NSPCs in Alzheimer's disease conditions. In this proposal, we will investigate the role of IL4 signaling in an Alzheimer mouse model, and will determine whether IL4 can act to restore the proliferative capacity of NSPCs in disease conditions. In overall, our investigations will be an important contribution to the neuroscience field as it has the potential to identify a neuroinflammatory crosstalk signal mechanism through IL4, which might impose proliferative ability to neural stem cells. Our work can contribute to regenerative medicine approaches in clinical efforts towards neurodegenerative diseases, and has the potential to constitute an important milestone for neuroinflammation research.

阿尔茨海默病是老年人中最常见的痴呆症；然而，目前还没有治愈这种疾病的方法。阿尔茨海默病的特点是大脑皮层中神经元和突触的慢性丧失，以及以进行性方式显著丧失脑质量。此外，有能力产生更多神经元的神经干/祖细胞停止增殖，因此不能产生更多的神经元。阿尔茨海默症患者大脑的所有这些特性都阻止了我们的大脑在疾病条件下成功再生。阿尔茨海默病再生治疗的一个重要方面是设计新颖和非常规的治疗方法。一种特殊的方法可能是调动内源性神经干细胞/祖细胞，以提高其增殖速度和分化能力。当结合旨在增加神经元存活和整合到神经回路的方法时，新生神经元水平的提高可能在高度不利的神经退行性环境中提供再生输入。因此，了解干细胞在神经变性过程中的行为，以及如何诱导它们产生更多的神经元是至关重要的。在斑马鱼中，我们已经确定了一种免疫相关分子IL4，它可以增加阿尔茨海默病条件下NSPCs的增殖。在这项提议中，我们将研究IL4信号在阿尔茨海默氏小鼠模型中的作用，并将确定IL4是否可以恢复疾病条件下NSPCs的增殖能力。总的来说，我们的研究将对神经科学领域做出重要贡献，因为它有可能通过il - 4确定神经炎症串扰信号机制，这可能会对神经干细胞的增殖能力产生影响。我们的工作可以促进再生医学方法在神经退行性疾病的临床努力，并有可能构成神经炎症研究的重要里程碑。