Chen Shuyan, Crack Peter J, Taylor Juliet M
Neuropharmacology Laboratory, Department of Biochemistry and Pharmacology, University of Melbourne, Parkville, Australia.
Brain Behav Immun Health. 2025 May 21;46:101017. doi: 10.1016/j.bbih.2025.101017. eCollection 2025 Jul.
Parkinson's disease (PD) is a chronic neurodegenerative disease characterized by motor dysfunction. Pathological hallmarks of the disease include selective dopaminergic neuronal death, intraneuronal deposits known as Lewy bodies and extensive neuroinflammation within the central nervous system (CNS). Microglia are the key cellular players in mediating this neuroinflammatory response, propagating this neuropathology to exacerbate the neuronal cell death. Growing evidence suggests a role for the type-I interferons (IFN) in driving the neuroinflammatory response in PD, with increased type-I IFN signatures reported in both PD patients and in animal models of the disease. This review will discuss 1) the key players that modulate the neuroinflammatory response in PD and their implications in the CNS 2) the contribution of the type-I IFNs in driving the neuroinflammatory response in PD, and 3) evidence for therapeutically targeting type-I IFN signalling to slow disease progression. A greater understanding of the underlying mechanisms that lead to the elevated neuroinflammatory response in PD could lead to new advances in therapeutic targets that effectively slow the disease progression.
帕金森病（PD）是一种以运动功能障碍为特征的慢性神经退行性疾病。该疾病的病理特征包括选择性多巴胺能神经元死亡、称为路易小体的神经元内沉积物以及中枢神经系统（CNS）内广泛的神经炎症。小胶质细胞是介导这种神经炎症反应的关键细胞成分，传播这种神经病理学以加剧神经元细胞死亡。越来越多的证据表明I型干扰素（IFN）在驱动PD中的神经炎症反应中起作用，在PD患者和该疾病的动物模型中均报告了I型IFN特征增加。本综述将讨论：1）调节PD中神经炎症反应的关键因素及其在中枢神经系统中的意义；2）I型IFN在驱动PD中神经炎症反应中的作用；3）靶向I型IFN信号传导以减缓疾病进展的治疗证据。对导致PD中神经炎症反应升高的潜在机制有更深入的了解，可能会在有效减缓疾病进展的治疗靶点方面取得新进展。
