Program of Computational Biology and Bioinformatics, Yale University, New Haven, CT, USA.
Department of Neurology, Yale University School of Medicine, New Haven, CT, USA.
Semin Immunopathol. 2022 Sep;44(5):659-672. doi: 10.1007/s00281-022-00947-3. Epub 2022 Jun 8.
Parkinson's disease (PD) is the second most common neurodegenerative disorder which affects 6.1 million people worldwide. The neuropathological hallmarks include the loss of dopaminergic neurons in the substantia nigra, the presence of Lewy bodies and Lewy neurites caused by α-synuclein aggregation, and neuroinflammation in the brain. The prodromal phase happens years before the onset of PD during which time many patients show gastro-intestinal symptoms. These symptoms are in support of Braak's theory and model where pathological α-synuclein propagates from the gut to the brain. Importantly, immune responses play a determinant role in the pathogenesis of Parkinson's disease. The innate immune responses triggered by microglia can cause neuronal death and disease progression. In addition, T cells infiltrate into the brains of PD patients and become involved in the adaptive immune responses. Interestingly, α-synuclein is associated with both innate and adaptive immune responses by directly interacting with microglia and T cells. Here, we give a detailed review of the immunobiology of Parkinson's disease, focusing on the role α-synuclein in the gut-brain axis hypothesis, the innate and adaptive immune responses involved in the disease, and current treatments.
帕金森病（PD）是第二常见的神经退行性疾病，影响全球 610 万人。神经病理学特征包括黑质中多巴胺能神经元的丧失、由α-突触核蛋白聚集引起的路易体和路易神经突的存在以及大脑中的神经炎症。前驱期发生在 PD 发病前数年，在此期间许多患者出现胃肠道症状。这些症状支持 Braak 的理论和模型，即病理性α-突触核蛋白从肠道传播到大脑。重要的是，免疫反应在帕金森病的发病机制中起决定作用。小胶质细胞引发的固有免疫反应可导致神经元死亡和疾病进展。此外，T 细胞浸润到 PD 患者的大脑中，并参与适应性免疫反应。有趣的是，α-突触核蛋白通过直接与小胶质细胞和 T 细胞相互作用，与固有和适应性免疫反应都有关联。在这里，我们详细回顾了帕金森病的免疫生物学，重点介绍了α-突触核蛋白在肠脑轴假说、疾病中涉及的固有和适应性免疫反应以及当前治疗方法中的作用。
