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帕金森病神经炎症的生物标志物。

Biomarker of Neuroinflammation in Parkinson's Disease.

机构信息

Linkou Medical Center, Department of Neurology, Chang Gung Memorial Hospital, Tauoyan 333, Taiwan.

School of Medicine, Chang Gung University, Taoyuan 333, Taiwan.

出版信息

Int J Mol Sci. 2022 Apr 8;23(8):4148. doi: 10.3390/ijms23084148.

Abstract

Parkinson's disease (PD) is caused by abnormal accumulation of α-synuclein in dopaminergic neurons of the substantia nigra, which subsequently causes motor symptoms. Neuroinflammation plays a vital role in the pathogenesis of neurodegeneration in PD. This neuroinflammatory neurodegeneration involves the activation of microglia, upregulation of proinflammatory factors, and gut microbiota. In this review, we summarized the recent findings on detection of PD by using inflammatory biomarkers, such as interleukin (IL)-1β, IL-2, IL-6, IL-10, tumor necrosis factor (TNF)-α; regulated upon activation, normal T cell expressed and presumably secreted (RANTES) and high-sensitivity c-reactive protein (hsCRP); and radiotracers such as [11C]PK11195 and [18F]-FEPPA, as well as by monitoring disease progression and the treatment response. Many PD-causing mutations in , , , , and are also associated with neuroinflammation. Several anti-inflammatory medications, including nonsteroidal anti-inflammatory drugs (NSAID), inhibitors of TNF-α and NLR family pyrin domain containing 3 (NLRP3), agonists of nuclear factor erythroid 2-related factor 2 (NRF2), peroxisome proliferator-activated receptor gamma (PPAR-γ), and steroids, have demonstrated neuroprotective effects in in vivo or in vitro PD models. Clinical trials applying objective biomarkers are required to investigate the therapeutic potential of anti-inflammatory medications for PD.

摘要

帕金森病(PD)是由黑质多巴胺能神经元中α-突触核蛋白异常积累引起的,随后导致运动症状。神经炎症在 PD 神经退行性变的发病机制中起着至关重要的作用。这种神经炎症性神经退行性变涉及小胶质细胞的激活、促炎因子的上调和肠道微生物群。在这篇综述中,我们总结了使用炎症生物标志物(如白细胞介素 (IL)-1β、IL-2、IL-6、IL-10、肿瘤坏死因子 (TNF)-α;激活调节正常 T 细胞表达和推测分泌 (RANTES) 和高敏 C 反应蛋白 (hsCRP);以及放射性示踪剂,如 [11C]PK11195 和 [18F]-FEPPA,以及监测疾病进展和治疗反应来检测 PD 的最新发现。 、 、 、 和 中的许多 PD 致病突变也与神经炎症有关。几种抗炎药物,包括非甾体抗炎药 (NSAID)、TNF-α 和 NLR 家族富含吡啶结构域蛋白 3 (NLRP3)抑制剂、核因子红细胞 2 相关因子 2 (NRF2)激动剂、过氧化物酶体增殖物激活受体 γ (PPAR-γ) 和类固醇,在体内或体外 PD 模型中显示出神经保护作用。需要应用客观生物标志物的临床试验来研究抗炎药物治疗 PD 的潜力。

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Neuroinflammation in Parkinson's Disease and its Treatment Opportunities.帕金森病中的神经炎症及其治疗机会。
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