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帕金森病中的炎症机制:从发病机制到靶向治疗

Inflammatory Mechanisms in Parkinson's Disease: From Pathogenesis to Targeted Therapies.

作者信息

Lee Stellina Y H, Yates Nathanael J, Tye Susannah J

机构信息

Queensland Brain Institute, The University of Queensland, Saint Lucia, Queensland, Australia.

Faculty of Medicine, The University of Queensland, Saint Lucia, Queensland, Australia.

出版信息

Neuroscientist. 2022 Oct;28(5):485-506. doi: 10.1177/1073858421992265. Epub 2021 Feb 13.

Abstract

Inflammation is a critical factor contributing to the progressive neurodegenerative process observed in Parkinson's disease (PD). Microglia, the immune cells of the central nervous system, are activated early in PD pathogenesis and can both trigger and propagate early disease processes via innate and adaptive immune mechanisms such as upregulated immune cells and antibody-mediated inflammation. Downstream cytokines and gene regulators such as microRNA (miRNA) coordinate later disease course and mediate disease progression. Biomarkers signifying the inflammatory and neurodegenerative processes at play within the central nervous system are of increasing interest to clinical teams. To be effective, such biomarkers must achieve the highest sensitivity and specificity for predicting PD risk, confirming diagnosis, or monitoring disease severity. The aim of this review was to summarize the current preclinical and clinical evidence that suggests that inflammatory processes contribute to the initiation and progression of neurodegenerative processes in PD. In this article, we further summarize the data about main inflammatory biomarkers described in PD to date and their potential for regulation as a novel target for disease-modifying pharmacological strategies.

摘要

炎症是帕金森病(PD)中进行性神经退行性变过程的一个关键因素。小胶质细胞作为中枢神经系统的免疫细胞,在PD发病机制早期就被激活,并可通过先天和适应性免疫机制(如免疫细胞上调和抗体介导的炎症)引发和传播早期疾病过程。下游细胞因子和基因调节因子,如微小RNA(miRNA),协调疾病后期进程并介导疾病进展。临床团队越来越关注能够表明中枢神经系统中炎症和神经退行性变过程的生物标志物。为了发挥作用,此类生物标志物必须在预测PD风险、确诊或监测疾病严重程度方面达到最高的敏感性和特异性。本综述的目的是总结当前的临床前和临床证据,这些证据表明炎症过程有助于PD中神经退行性变过程的起始和进展。在本文中,我们进一步总结了迄今为止在PD中描述的主要炎症生物标志物的数据及其作为疾病修饰药理学策略新靶点的调节潜力。

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