Lin Zhuomiao, Yu Xihui, Zhong Yunming, Tan Guozhu, Zhong Jiahong
Department of Clinical Pharmacy, Meizhou People's Hospital (Huangtang Hospital), Meizhou, Guangdong, China.
Department of Pharmacy, The Second Affiliated Hospital of Shantou University Medical College, Shantou, Guangdong, China.
PeerJ. 2025 Aug 14;13:e19818. doi: 10.7717/peerj.19818. eCollection 2025.
Current pharmacological treatment of Parkinson's disease (PD) predominantly employs dopaminergic agents aimed at enhancing cerebral dopamine levels. While these therapeutic strategies provide symptomatic relief, their palliative nature is frequently associated with dose-dependent complications, including gastrointestinal disturbances, emetic symptoms, and motor complications such as dyskinesia. Moreover, the honeymoon period of drugs has greatly limited their clinical application. The multifactorial etiology of PD continues to challenge researchers, yet substantial evidence implicates α-synuclein as a critical pathogenic mediator. Emerging findings suggest that dysregulated neuroimmune interactions constitute a fundamental mechanism in PD progression, where chronic immune activation appears particularly detrimental to neuronal survival. Notably, neuroinflammatory cascades coupled with compromised blood-brain barrier (BBB) integrity create a self-perpetuating cycle of neural degeneration, wherein α-synuclein-specific T cells exacerbate disease pathology while regulatory T cell populations demonstrate potential immunomodulatory capacities. This review systematically examines the mechanistic interplay involving neuroinflammatory cascades, BBB compromise, central nervous system (CNS) immunoregulation, and T lymphocyte subpopulations (including regulatory T cells) in the pathogenesis of PD. By synthesizing current evidence, we aim to establish a conceptual framework supporting the investigation of cellular immunity-based therapies for PD.
目前帕金森病(PD)的药物治疗主要采用旨在提高脑内多巴胺水平的多巴胺能药物。虽然这些治疗策略能缓解症状,但其姑息性往往与剂量依赖性并发症相关,包括胃肠道紊乱、呕吐症状以及运动并发症如运动障碍。此外,药物的蜜月期极大地限制了它们的临床应用。PD的多因素病因继续给研究人员带来挑战,但大量证据表明α-突触核蛋白是关键的致病介质。新出现的研究结果表明,神经免疫相互作用失调是PD进展的一个基本机制,其中慢性免疫激活似乎对神经元存活特别有害。值得注意的是,神经炎症级联反应加上血脑屏障(BBB)完整性受损,形成了一个神经退行性变的自我延续循环,其中α-突触核蛋白特异性T细胞会加剧疾病病理,而调节性T细胞群体则表现出潜在的免疫调节能力。本综述系统地研究了神经炎症级联反应、BBB破坏、中枢神经系统(CNS)免疫调节和T淋巴细胞亚群(包括调节性T细胞)在PD发病机制中的机制相互作用。通过综合现有证据,我们旨在建立一个概念框架,以支持对基于细胞免疫的PD治疗方法的研究。