Cintia Roodveldt, Liliana Bernardino, Ozgur Oztop-Cakmak, Milorad Dragic, Kari E Fladmark, Sibel Ertan, Busra Aktas, Carlos Pita, Lucia Ciglar, Gaetan Garraux, Caroline Williams-Gray, Rodrigo Pacheco, Marina Romero-Ramos
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引用次数: 0
Abstract
Parkinson's disease is characterized neuropathologically by the degeneration of dopaminergic neurons in the ventral midbrain, the accumulation of α-synuclein (α-syn) aggregates in neurons and chronic neuroinflammation. In the past two decades, in vitro, ex vivo and in vivo studies have consistently shown the involvement of inflammatory responses mediated by microglia and astrocytes, which may be elicited by pathological α-syn or signals from affected neurons and other cell types, and are directly linked to neurodegeneration and disease development. Apart from the prominent immune alterations seen in the CNS, including the infiltration of T cells into the brain, more recent studies have demonstrated important changes in the peripheral immune profile within both the innate and adaptive compartments, particularly involving monocytes, CD4+ and CD8+ T cells. This review aims to integrate the consolidated understanding of immune-related processes underlying the pathogenesis of Parkinson's disease, focusing on both central and peripheral immune cells, neuron-glia crosstalk as well as the central-peripheral immune interaction during the development of Parkinson's disease. Our analysis seeks to provide a comprehensive view of the emerging knowledge of the mechanisms of immunity in Parkinson's disease and the implications of this for better understanding the overall pathogenesis of this disease.
帕金森病(PD)的神经病理学特征是腹侧中脑多巴胺能神经元变性、α-突触核蛋白(α-syn)聚集在神经元中以及慢性神经炎症。在过去的二十年中,体外、体内和体外研究不断表明,由小胶质细胞和星形胶质细胞介导的炎症反应可能由病理α-syn或来自受影响神经元和其他细胞类型的信号诱发,并与神经变性和疾病发展直接相关。除了中枢神经系统(CNS)中出现的显著免疫改变(包括 T 细胞向大脑的浸润)外,最近的研究还表明,先天性和适应性分区中的外周免疫特征也发生了重要变化,尤其是涉及单核细胞、CD4+ 和 CD8+ T 细胞。本综述旨在整合对帕金森氏症发病机制中免疫相关过程的综合认识,重点关注中枢和外周免疫细胞、神经元-胶质细胞串联以及帕金森氏症发病过程中中枢-外周免疫相互作用。我们的分析旨在提供有关帕金森病免疫机制的新知识的综合视角,以及这些知识对更好地理解该疾病整体发病机制的影响。
期刊介绍:
Brain, a journal focused on clinical neurology and translational neuroscience, has been publishing landmark papers since 1878. The journal aims to expand its scope by including studies that shed light on disease mechanisms and conducting innovative clinical trials for brain disorders. With a wide range of topics covered, the Editorial Board represents the international readership and diverse coverage of the journal. Accepted articles are promptly posted online, typically within a few weeks of acceptance. As of 2022, Brain holds an impressive impact factor of 14.5, according to the Journal Citation Reports.