Periphery and brain, innate and adaptive immunity in Parkinson's disease.
Periphery and brain, innate and adaptive immunity in Parkinson's disease.
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DOI：
10.1007/s00401-021-02268-5
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发表时间：
2021-04
影响因子：
12.7
通讯作者：
Romero-Ramos M
中科院分区：
文献类型：
--
作者：
Harms AS;Ferreira SA;Romero-Ramos M
帕金森病（PD）是一种神经退行性疾病，其中α-突触核蛋白在中枢神经系统以及外周神经系统中的神经元的死亡和功能障碍中起核心作用。除了在患者中观察到的神经元事件外，PD还包括重要的免疫成分。这表明PD相关的免疫反应将对神经元健康产生影响，因此开放免疫调节作为PD的潜在治疗策略。疾病期间的免疫变化发生在大脑中，涉及小胶质细胞，但也发生在外周中，先天免疫系统的细胞，特别是单核细胞，以及适应性免疫的细胞，如T细胞。这一认识来自多个患者研究，也来自疾病动物模型的数据，为PD中枢神经系统和外周的先天性和适应性免疫系统串扰提供了强有力的证据。在这里，我们回顾的数据表明，α-突触核蛋白在激活先天性和适应性免疫系统中起着至关重要的作用。我们还将描述表明PD中的炎症包括先天性和适应性免疫细胞的早期变化的研究，这些免疫细胞在疾病期间随着时间的推移动态发展，导致患者的神经元变性和神经变性。这一新的发现有助于将PD定义为一种多系统疾病，应该以更整合的方式而不是以大脑为中心的经典方法来处理。
Parkinson’s disease (PD) is a neurodegenerative disorder where alpha-synuclein plays a central role in the death and dysfunction of neurons, both, in central, as well as in the peripheral nervous system. Besides the neuronal events observed in patients, PD also includes a significant immune component. It is suggested that the PD-associated immune response will have consequences on neuronal health, thus opening immunomodulation as a potential therapeutic strategy in PD. The immune changes during the disease occur in the brain, involving microglia, but also in the periphery with changes in cells of the innate immune system, particularly monocytes, as well as those of adaptive immunity, such as T-cells. This realization arises from multiple patient studies, but also from data in animal models of the disease, providing strong evidence for innate and adaptive immune system crosstalk in the central nervous system and periphery in PD. Here we review the data showing that alpha-synuclein plays a crucial role in the activation of the innate and adaptive immune system. We will also describe the studies suggesting that inflammation in PD includes early changes in innate and adaptive immune cells that develop dynamically through time during disease, contributing to neuronal degeneration and symptomatology in patients. This novel finding has contributed to the definition of PD as a multisystem disease that should be approached in a more integratory manner rather than a brain-focused classical approach.
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