Storelli Elisa, Cassina Niccolò, Rasini Emanuela, Marino Franca, Cosentino Marco
Center of Research in Medical Pharmacology, University of Insubria, Varese, Italy.
Front Neurol. 2019 Jan 24;10:13. doi: 10.3389/fneur.2019.00013. eCollection 2019.
Parkinson's disease (PD) is a neurodegenerative disease characterized by progressive loss of dopaminergic neurons, appearance of Lewy bodies and presence of neuroinflammation. No treatments currently exist to prevent PD or delay its progression, and dopaminergic substitution treatments just relieve the consequences of dopaminergic neuron loss. Increasing evidence points to peripheral T lymphocytes as key players in PD, and recently there has been growing interest into the specific role of T helper (Th) 17 lymphocytes. Th17 are a proinflammatory CD4+ T cell lineage named after interleukin (IL)-17, the main cytokine produced by these cells. Th17 are involved in immune-related disease such as psoriasis, rheumatoid arthritis and inflammatory bowel disease, and drugs targeting Th17/IL-17 are currently approved for clinical use in such disease. In the present paper, we first summarized current knowledge about contribution of the peripheral immune system in PD, as well as about the physiopharmacology of Th17 and IL-17 together with its therapeutic relevance. Thereafter, we systematically retrieved and evaluated published evidence about Th17 and IL-17 in PD, to help assessing Th17/IL-17-targeting drugs as potentially novel antiparkinson agents. Critical appraisal of the evidence did not allow to reach definite conclusions: both animal as well as clinical studies are limited, just a few provide mechanistic evidence and none of them investigates the eventual relationship between Th17/IL-17 and clinically relevant endpoints such as disease progression, disability scores, intensity of dopaminergic substitution treatment. Careful assessment of Th17 in PD is anyway a priority, as Th17/IL-17-targeting therapeutics might represent a straightforward opportunity for the unmet needs of PD patients.
帕金森病（PD）是一种神经退行性疾病，其特征为多巴胺能神经元进行性丧失、路易小体出现以及神经炎症存在。目前尚无预防PD或延缓其进展的治疗方法，多巴胺能替代治疗仅能缓解多巴胺能神经元丧失的后果。越来越多的证据表明外周T淋巴细胞是PD的关键因素，最近人们对辅助性T（Th）17淋巴细胞的具体作用越来越感兴趣。Th17是一种促炎性CD4 + T细胞谱系，以白细胞介素（IL）-17命名，IL-17是这些细胞产生的主要细胞因子。Th17参与免疫相关疾病，如银屑病、类风湿性关节炎和炎症性肠病，目前靶向Th17 / IL-17的药物已被批准用于此类疾病的临床治疗。在本文中，我们首先总结了关于外周免疫系统在PD中的作用的现有知识，以及Th17和IL-17的生理药理学及其治疗相关性。此后，我们系统地检索和评估了已发表的关于PD中Th17和IL-17的证据，以帮助评估靶向Th17 / IL-17的药物作为潜在的新型抗帕金森病药物。对证据的批判性评估无法得出明确结论：动物研究和临床研究都很有限，只有少数提供了机制证据，而且没有一项研究调查Th17 / IL-17与疾病进展、残疾评分、多巴胺能替代治疗强度等临床相关终点之间的最终关系。无论如何，仔细评估PD中的Th17是当务之急，因为靶向Th17 / IL-17的疗法可能为满足PD患者未满足的需求提供直接机会。
