Jo Min Gi, Kim Seon-Hee, Yun Seung Pil
Department of Pathology, College of Medicine, Kyung Hee University, Seoul, Republic of Korea.
Department of Pharmacology, Institute of Medical Sciences, College of Medicine, Gyeongsang National University, Jinju, Republic of Korea.
Neural Regen Res. 2024 Dec 16;21(1):57-61. doi: 10.4103/NRR.NRR-D-24-01063.
Parkinson's disease is a neurodegenerative disorder marked by the degeneration of dopaminergic neurons and clinical symptoms such as tremors, rigidity, and slowed movements. A key feature of Parkinson's disease is the accumulation of misfolded α-synuclein, forming insoluble Lewy bodies in the substantia nigra pars compacta, which contributes to neurodegeneration. These α-synuclein aggregates may act as autoantigens, leading to T-cell-mediated neuroinflammation and contributing to dopaminergic cell death. Our perspective explores the hypothesis that Parkinson's disease may have an autoimmune component, highlighting research that connects peripheral immune responses with neurodegeneration. T cells derived from Parkinson's disease patients appear to have the potential to initiate an autoimmune response against α-synuclein and its modified peptides, possibly leading to the formation of neo-epitopes. Recent evidence associates Parkinson's disease with abnormal immune responses, as indicated by increased levels of immune cells, such as CD4+ and CD8+ T cells, observed in both patients and mouse models. The convergence of T cells filtration increasing major histocompatibility complex molecules, and the susceptibility of dopaminergic neurons supports the hypothesis that Parkinson's disease may exhibit autoimmune characteristics. Understanding the immune mechanisms involved in Parkinson's disease will be crucial for developing therapeutic strategies that target the autoimmune aspects of the disease. Novel approaches, including precision medicine based on major histocompatibility complex/human leukocyte antigen typing and early biomarker identification, could pave the way for immune-based treatments aimed at slowing or halting disease progression. This perspective explores the relationship between autoimmunity and Parkinson's disease, suggesting that further research could deepen understanding and offer new therapeutic avenues. In this paper, it is organized to provide a comprehensive perspective on the autoimmune aspects of Parkinson's disease. It investigates critical areas such as the autoimmune response observed in Parkinson's disease patients and the role of autoimmune mechanisms targeting α-synuclein in Parkinson's disease. The paper also examines the impact of CD4+ T cells, specifically Th1 and Th17, on neurons through in-vitro and ex-vivo studies. Additionally, it explores how α-synuclein influences glia-induced neuroinflammation in Parkinson's disease. The discussion extends to the clinical implications and therapeutic landscape, offering insights into potential treatments. Consequently, we aim to provide a comprehensive perspective on the autoimmune aspects of Parkinson's disease, incorporating both supportive and opposing views on its classification as an autoimmune disorder and exploring implications for clinical applications.
帕金森病是一种神经退行性疾病，其特征是多巴胺能神经元退化以及出现震颤、僵硬和运动迟缓等临床症状。帕金森病的一个关键特征是错误折叠的α-突触核蛋白积累，在黑质致密部形成不溶性路易小体，这会导致神经退行性变。这些α-突触核蛋白聚集体可能作为自身抗原，引发T细胞介导的神经炎症并导致多巴胺能细胞死亡。我们的观点探讨了帕金森病可能具有自身免疫成分的假说，强调了将外周免疫反应与神经退行性变联系起来的研究。帕金森病患者来源的T细胞似乎有引发针对α-突触核蛋白及其修饰肽的自身免疫反应的潜力，这可能导致新表位的形成。最近的证据将帕金森病与异常免疫反应联系起来，患者和小鼠模型中均观察到免疫细胞（如CD4+和CD8+ T细胞）水平升高。T细胞过滤增加主要组织相容性复合体分子以及多巴胺能神经元的易感性，支持了帕金森病可能具有自身免疫特征的假说。了解帕金森病中涉及的免疫机制对于制定针对该疾病自身免疫方面的治疗策略至关重要。包括基于主要组织相容性复合体/人类白细胞抗原分型的精准医学和早期生物标志物识别在内的新方法，可能为旨在减缓或阻止疾病进展的免疫治疗铺平道路。这一观点探讨了自身免疫与帕金森病之间的关系，表明进一步的研究可能会加深理解并提供新的治疗途径。本文旨在全面阐述帕金森病自身免疫方面的情况。它研究了关键领域，如帕金森病患者中观察到的自身免疫反应以及帕金森病中针对α-突触核蛋白的自身免疫机制的作用。本文还通过体外和离体研究考察了CD4+ T细胞，特别是Th1和Th17对神经元的影响。此外，它探讨了α-突触核蛋白如何影响帕金森病中胶质细胞诱导的神经炎症。讨论延伸到临床意义和治疗前景，为潜在治疗提供见解。因此，我们旨在全面阐述帕金森病自身免疫方面的情况，纳入关于其作为自身免疫性疾病分类的支持和反对观点，并探讨对临床应用的影响。
