Fang Kevin
Living Systems Institute University Exeter Exeter UK.
Ibrain. 2024 Dec 2;10(4):462-476. doi: 10.1002/ibra.12185. eCollection 2024 Winter.
The immune response in the central nervous system (CNS) is a highly specialized and tightly regulated process essential for maintaining neural health and protecting against pathogens and injuries. The primary immune cells within the CNS include microglia, astrocytes, T cells, and B cells. They work together, continuously monitor the CNS environment for signs of infection, injury, or disease, and respond by phagocytosing debris, releasing cytokines, and recruiting other immune cells. In addition to providing neuroprotection, these immune responses must be carefully balanced to prevent excessive inflammation that can lead to neuronal damage and contribute to neurodegenerative diseases. Dysregulated immune responses in the CNS are implicated in various neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis. Wnt signaling is a crucial pathway in the CNS that regulates various cellular processes critical for brain development, function, and maintenance. Despite enhancing immune responses in the health CNS, dysregulated Wnt signaling exacerbates neuroinflammation in the neurodegenerative brains. This review summarized the role of Wnt signaling in regulating immune response under different conditions. We then examined the role of immune response in healthy brains and during the development of neurodegenerative diseases. We also discussed therapeutic intervention in various neurodegenerative diseases through the modulation of the Wnt signaling pathway and neuroinflammation and highlighted challenges and limitations in current clinical trials.
中枢神经系统（CNS）中的免疫反应是一个高度专业化且受到严格调控的过程，对于维持神经健康以及抵御病原体和损伤至关重要。中枢神经系统内的主要免疫细胞包括小胶质细胞、星形胶质细胞、T细胞和B细胞。它们协同工作，持续监测中枢神经系统环境，以寻找感染、损伤或疾病的迹象，并通过吞噬碎片、释放细胞因子以及招募其他免疫细胞做出反应。除了提供神经保护作用外，这些免疫反应必须仔细平衡，以防止过度炎症，否则可能导致神经元损伤并引发神经退行性疾病。中枢神经系统中失调的免疫反应与各种神经退行性疾病有关，如阿尔茨海默病、帕金森病和肌萎缩侧索硬化症。Wnt信号通路是中枢神经系统中的一条关键途径，它调节着对大脑发育、功能和维持至关重要的各种细胞过程。尽管Wnt信号通路在健康的中枢神经系统中增强免疫反应，但失调的Wnt信号通路会加剧神经退行性大脑中的神经炎症。这篇综述总结了Wnt信号通路在不同条件下调节免疫反应中的作用。然后，我们研究了免疫反应在健康大脑以及神经退行性疾病发展过程中的作用。我们还讨论了通过调节Wnt信号通路和神经炎症对各种神经退行性疾病进行的治疗干预，并强调了当前临床试验中的挑战和局限性。
