Centre for Molecular Biology and Regenerative Medicine-CABIMER, University of Seville-CSIC, Seville 41092, Spain.
Department of Medical Biochemistry, Molecular Biology and Immunology, Faculty of Medicine, University of Seville, Seville 41009, Spain.
Brain. 2024 Oct 3;147(10):3306-3324. doi: 10.1093/brain/awae177.
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.
帕金森病的神经病理学特征是腹侧中脑中多巴胺能神经元的退化、神经元中α-突触核蛋白(α-syn)聚集物的积累和慢性神经炎症。在过去的二十年中,体外、离体和体内研究一致表明,小胶质细胞和星形胶质细胞介导的炎症反应的参与,这可能是由病理性α-syn 或受影响神经元和其他细胞类型的信号引发的,并且与神经退行性变和疾病发展直接相关。除了中枢神经系统中明显的免疫改变,包括 T 细胞浸润大脑,最近的研究还表明,固有和适应性免疫成分中,外周免疫特征发生了重要变化,特别是涉及单核细胞、CD4+和 CD8+T 细胞。本综述旨在整合对帕金森病发病机制中与免疫相关的过程的综合认识,重点关注中枢和外周免疫细胞、神经元-胶质细胞相互作用以及帕金森病发展过程中的中枢-外周免疫相互作用。我们的分析旨在提供对帕金森病免疫机制的新兴知识的全面了解,以及这对更好地理解这种疾病的整体发病机制的意义。
Brain. 2024-10-3
Eur J Neurosci. 2018-12-10
Pharmacol Res. 2024-5
Int J Mol Sci. 2021-6-17
NeuroImmune Pharm Ther. 2025-6-20
Neurosci Bull. 2025-6-25
Behav Brain Funct. 2025-5-31
Nat Rev Neurol. 2025-5-22
Pharmacol Rev. 2023-12-15
Cell Mol Life Sci. 2023-6-30