Department of Pathology, VU University Medical Centre, Amsterdam, the Netherlands; Neuroimmunology Unit, Blizard Institute of Cell and Molecular Science, Barts and The London School of Medicine and Dentistry, London, UK.
Immunology. 2014 Jun;142(2):151-66. doi: 10.1111/imm.12233.
Neurodegeneration, the progressive dysfunction and loss of neurons in the central nervous system (CNS), is the major cause of cognitive and motor dysfunction. While neuronal degeneration is well-known in Alzheimer's and Parkinson's diseases, it is also observed in neurotrophic infections, traumatic brain and spinal cord injury, stroke, neoplastic disorders, prion diseases, multiple sclerosis and amyotrophic lateral sclerosis, as well as neuropsychiatric disorders and genetic disorders. A common link between these diseases is chronic activation of innate immune responses including those mediated by microglia, the resident CNS macrophages. Such activation can trigger neurotoxic pathways leading to progressive degeneration. Yet, microglia are also crucial for controlling inflammatory processes, and repair and regeneration. The adaptive immune response is implicated in neurodegenerative diseases contributing to tissue damage, but also plays important roles in resolving inflammation and mediating neuroprotection and repair. The growing awareness that the immune system is inextricably involved in mediating damage as well as regeneration and repair in neurodegenerative disorders, has prompted novel approaches to modulate the immune system, although it remains whether these approaches can be used in humans. Additional factors in humans include ageing and exposure to environmental factors such as systemic infections that provide additional clues that may be human specific and therefore difficult to translate from animal models. Nevertheless, a better understanding of how immune responses are involved in neuronal damage and regeneration, as reviewed here, will be essential to develop effective therapies to improve quality of life, and mitigate the personal, economic and social impact of these diseases.
神经退行性病变，即中枢神经系统（CNS）中神经元的进行性功能障碍和丧失，是认知和运动功能障碍的主要原因。虽然神经元退化在阿尔茨海默病和帕金森病中众所周知，但在神经营养性感染、创伤性脑和脊髓损伤、中风、肿瘤性疾病、朊病毒病、多发性硬化症和肌萎缩侧索硬化症以及神经精神障碍和遗传疾病中也观察到这种退化。这些疾病之间的一个共同联系是固有免疫反应的慢性激活，包括小胶质细胞（中枢神经系统的固有巨噬细胞）介导的反应。这种激活可以触发导致进行性退化的神经毒性途径。然而，小胶质细胞对于控制炎症过程以及修复和再生也是至关重要的。适应性免疫反应与神经退行性疾病有关，导致组织损伤，但也在炎症的解决以及神经保护和修复中发挥重要作用。越来越多的人认识到免疫系统在介导神经退行性疾病中的损伤以及再生和修复中不可分割的作用，这促使人们采用新的方法来调节免疫系统，尽管这些方法是否可以用于人类仍存在争议。人类的其他因素包括衰老和暴露于环境因素，如全身性感染，这些因素提供了额外的线索，这些线索可能是人类特有的，因此很难从动物模型中转化。然而，如本文所综述的，更好地了解免疫反应如何参与神经元损伤和再生，对于开发有效的治疗方法以提高生活质量、减轻这些疾病对个人、经济和社会的影响至关重要。
