Local control of inflammation neuronal damage by Peroxisome-profilator-activated receptory (PPARy) in EAE

过氧化物酶体延长物激活受体 (PPARy) 对 EAE 中炎症神经元损伤的局部控制

• 批准号: 50356369
• 负责人: Professorin Dr. Luisa Klotz
• 金额: --
• 依托单位: Klinik und Poliklinik für Neurologie
• 依托单位国家: 德国
• 项目类别: Clinical Research Units
• 财政年份: 2007
• 资助国家: 德国
• 起止时间: 2006-12-31 至 2013-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/50356369?language=en
• 关键词: Local; control; inflammation; neuronal; damage

During the last funding period, we were able to show that ablation of the nuciear receptor PPARy in myeloid cells enhances CNS inflammation during the effector phase of EAE, which was associated with an increased activation status of PPARy-ablated cells within the CNS. We now plan to further explore the protective effects of PPARy on inflammation-associated neuronal damage. We propose the existence of a PPARy-mediated neuroprotective cross-talk between local immune cells and neurons within the CNS. First, we will determine the protective influence of PPARy in microglia and invading monocytes on inflammation-induced neuronal damage in brain slice cultures. We will assess whether PPARy results in altematively activated macrophages and microglial cells exhibiting anti-inflammatory and neuroprotective properties. Moreover, we plan to identify the functional relevance of endogenous PPARy ligands produced locally within the CNS for the generation of a neuroprotective milieu and alleviation of inflammation-induced neurotoxicity in vivo. Together, our study will help to identify the therapeutic potential of PPARy in myeloid cells for targeting CNS autoimmunity by enhancing neuroprotective interactions between immune cells and neuronal cells.

在最后一个资助期，我们能够证明，在EAE的效应期，髓样细胞中核受体PPARy的消融增强了CNS炎症，这与CNS内PPARy消融细胞的活化状态增加有关。我们现在计划进一步探索PPARy对炎症相关神经元损伤的保护作用。我们提出中枢神经系统内局部免疫细胞和神经元之间存在PPARy介导的神经保护性串扰。首先，我们将确定小胶质细胞和侵入单核细胞中的PPARy对脑切片培养物中炎症诱导的神经元损伤的保护作用。我们将评估PPARy是否导致交替活化的巨噬细胞和小胶质细胞表现出抗炎和神经保护特性。此外，我们计划鉴定在CNS内局部产生的内源性PPARy配体的功能相关性，用于产生神经保护环境和减轻体内炎症诱导的神经毒性。总之，我们的研究将有助于确定骨髓细胞中的PPARy通过增强免疫细胞和神经元细胞之间的神经保护性相互作用来靶向CNS自身免疫的治疗潜力。