Center for Neurology, Department of Parkinson, Sleep and Movement Disorders, University Hospital Bonn, 53127 Bonn, Germany; Institute of Physiology II, University Hospital Bonn, 53115 Bonn, Germany.
Luxembourg Centre for Systems Biomedicine, University of Luxembourg, Belval, Luxembourg; Division of Infectious Diseases and Immunology, University of Massachusetts Medical School, Worcester, MA, USA.
Immunity. 2024 Apr 9;57(4):790-814. doi: 10.1016/j.immuni.2024.03.010.
Activation of the innate immune system following pattern recognition receptor binding has emerged as one of the major pathogenic mechanisms in neurodegenerative disease. Experimental, epidemiological, pathological, and genetic evidence underscores the meaning of innate immune activation during the prodromal as well as clinical phases of several neurodegenerative disorders including Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, and frontotemporal dementia. Importantly, innate immune activation and the subsequent release of inflammatory mediators contribute mechanistically to other hallmarks of neurodegenerative diseases such as aberrant proteostatis, pathological protein aggregation, cytoskeleton abnormalities, altered energy homeostasis, RNA and DNA defects, and synaptic and network disbalance and ultimately to the induction of neuronal cell death. In this review, we discuss common mechanisms of innate immune activation in neurodegeneration, with particular emphasis on the pattern recognition receptors (PRRs) and other receptors involved in the detection of damage-associated molecular patterns (DAMPs).
固有免疫系统的激活是神经退行性疾病的主要发病机制之一，这是继模式识别受体结合之后得出的结论。实验、流行病学、病理学和遗传学证据强调了固有免疫激活在几种神经退行性疾病的前驱期和临床期的重要性，包括阿尔茨海默病、帕金森病、肌萎缩侧索硬化症和额颞叶痴呆。重要的是，固有免疫激活和随后炎症介质的释放从机制上导致了神经退行性疾病的其他特征，如异常的蛋白稳态、病理性蛋白聚集、细胞骨架异常、能量代谢失衡、RNA 和 DNA 缺陷以及突触和网络失衡，并最终导致神经元细胞死亡。在这篇综述中，我们讨论了神经退行性变中固有免疫激活的常见机制，特别强调了参与检测损伤相关分子模式（DAMPs）的模式识别受体（PRRs）和其他受体。
