The role of immunoproteasomes and the ubiquitin system in inflammatory processes in mouse models of Alzheimer's and Parkinson's disease (B07+)

免疫蛋白酶体在清除受损蛋白以维持炎症过程中的蛋白稳定方面起着重要作用。受损蛋白质的积累、聚集和随后的细胞死亡以及神经炎症是神经退行性变的特征。该项目旨在研究免疫蛋白酶体缺陷对阿尔茨海默病和帕金森病小鼠模型神经炎症和疾病进展的影响。由于免疫蛋白酶体损伤导致自身炎症和显著的I型干扰素特征，将从细胞因子谱、小胶质细胞激活、其与氧化应激和蛋白质包涵体的相关性以及神经元的可塑性等方面研究这种联系。

Immunoproteasomes play an important role in the clearance of damaged proteins to maintain proteostasis during inflammation. The accumulation of damaged proteins, their aggregation, and subsequent cell death along with neuroinflammation represent hallmarks of neurodegeneration. The project aims to investigate the impact of immunoproteasome deficiency on neuroinflammation and disease progression in mouse models of Alzheimer`s and Parkinson`s disease. As immunoproteasome impairment results in autoinflammation along with a striking type I interferon signature, this link will be studied in terms of cytokine profiles, microglia activation, its association with oxidative stress and protein inclusions, as well as neuronal plasticity.