Cabrera Ranaldi Erika D L R M, Nuytemans Karen, Martinez Anisley, Luca Corneliu C, Keane Robert W, de Rivero Vaccari Juan Pablo
Department of Neurological Surgery and The Miami Project to Cure Paralysis, University of Miami Miller School of Medicine, Miami, FL 33136, USA.
The Dr. John T. Macdonald Foundation, Department of Human Genetics, University of Miami Miller School of Medicine, Miami, FL 33136, USA.
Pharmaceuticals (Basel). 2023 Jun 15;16(6):883. doi: 10.3390/ph16060883.
Parkinson's disease (PD) is a neurodegenerative disorder marked by the death of dopaminergic neurons in the midbrain, the accumulation of α-synuclein aggregates, and motor deficits. A major contributor to dopaminergic neuronal loss is neuroinflammation. The inflammasome is a multiprotein complex that perpetuates neuroinflammation in neurodegenerative disorders including PD. Increases in inflammasome proteins are associated with worsened pathology. Thus, the inhibition of inflammatory mediators has the potential to aid in PD treatment. Here, we investigated inflammasome signaling proteins as potential biomarkers of the inflammatory response in PD. Plasma from PD subjects and healthy age-matched controls were evaluated for levels of the inflammasome protein apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC), caspase-1, and interleukin (IL)-18. This was carried out using Simple Plex technology to identify changes in inflammasome proteins in the blood of PD subjects. The area under the curve (AUC) was obtained through calculation of the receiver operating characteristics (ROC) to obtain information on biomarker reliability and traits. Additionally, we completed a stepwise regression selected from the lowest Akaike information criterion (AIC) to assess how the inflammasome proteins caspase-1 and ASC contribute to IL-18 levels in people with PD. PD subjects demonstrated elevated caspase-1, ASC, and IL-18 levels when compared to controls; each of these proteins were found to be promising biomarkers of inflammation in PD. Furthermore, inflammasome proteins were determined to significantly contribute to and predict IL-18 levels in subjects with PD. Thus, we demonstrated that inflammasome proteins serve as reliable biomarkers of inflammation in PD and that inflammasome proteins provide significant contributions to IL-18 levels in PD.
帕金森病（PD）是一种神经退行性疾病，其特征是中脑多巴胺能神经元死亡、α-突触核蛋白聚集体积累以及运动功能障碍。多巴胺能神经元损失的一个主要促成因素是神经炎症。炎性小体是一种多蛋白复合物，在包括PD在内的神经退行性疾病中会使神经炎症持续存在。炎性小体蛋白的增加与病理状况恶化有关。因此，抑制炎症介质有可能有助于PD的治疗。在此，我们研究了炎性小体信号蛋白作为PD炎症反应潜在生物标志物的情况。对PD患者和年龄匹配的健康对照者的血浆进行评估，检测炎性小体蛋白含半胱天冬酶募集结构域的凋亡相关斑点样蛋白（ASC）、半胱天冬酶-1和白细胞介素（IL）-18的水平。这是使用Simple Plex技术来确定PD患者血液中炎性小体蛋白的变化。通过计算受试者工作特征曲线（ROC）获得曲线下面积（AUC），以获取有关生物标志物可靠性和特征的信息。此外，我们完成了从最低赤池信息准则（AIC）中选择的逐步回归分析，以评估炎性小体蛋白半胱天冬酶-1和ASC如何影响PD患者的IL-18水平。与对照组相比，PD患者的半胱天冬酶-1、ASC和IL-18水平升高；这些蛋白中的每一种都被发现是PD炎症的有前景的生物标志物。此外，炎性小体蛋白被确定对PD患者的IL-18水平有显著贡献并可对其进行预测。因此，我们证明炎性小体蛋白是PD炎症的可靠生物标志物，并且炎性小体蛋白对PD患者的IL-18水平有显著贡献。
