Meta-Analysis of the Mechanisms Underlying COVID-19 Modulation of Parkinson's Disease.
Meta-Analysis of the Mechanisms Underlying COVID-19 Modulation of Parkinson's Disease.
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DOI：
10.3390/ijms241713554
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发表时间：
2023-08-31
影响因子：
5.6
通讯作者：
中科院分区：
文献类型：
--
作者：
冠状病毒病-19（COVID-19）是由严重急性呼吸道综合征-冠状病毒-2（SARS-CoV-2）感染引起的。病毒通过受体介导的血管紧张素转换酶-2（ACE 2）内吞作用进入宿主细胞，导致全身性炎症（也称为“细胞因子风暴”）和神经炎症。COVID-19的上游调节因子干扰素-γ（IFNG）在SARS-CoV-2感染后下调，导致ACE 2下调。神经炎症信号通路（NISP）可导致神经退行性疾病，如帕金森病（PD），其特征在于形成主要由突触核蛋白α（SNCA）基因编码的α-突触核蛋白蛋白组成的路易体。我们假设COVID-19可能通过细胞因子风暴诱导的神经炎症调节PD进展。本研究旨在阐明与PD等神经退行性疾病相关的COVID-19触发病理学的可能机制和信号通路。本研究分析了SARS-CoV-2感染后ACE 2下调的途径及其对PD进展的影响。通过QIAGEN的不相容性通路分析（IPA），该研究确定NISP为前五位的经典通路/信号通路，SNCA为前五位的上游调节因子。还对COVID-19和SNCA之间的相关分子进行了核心分析，以构建网络连接图。分子活性预测器工具用于通过下调IFNG来模拟SARS-CoV-2的感染，从而通过中间分子数据集预测SNCA的激活，随后导致PD的激活。下游效应分析进一步用于量化ACE 2对SNCA激活的下调。
Coronavirus disease-19 (COVID-19) is caused by the infection of severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2). The virus enters host cells through receptor-mediated endocytosis of angiotensin-converting enzyme-2 (ACE2), leading to systemic inflammation, also known as a “cytokine storm”, and neuroinflammation. COVID-19’s upstream regulator, interferon-gamma (IFNG), is downregulated upon the infection of SARS-CoV-2, which leads to the downregulation of ACE2. The neuroinflammation signaling pathway (NISP) can lead to neurodegenerative diseases, such as Parkinson’s disease (PD), which is characterized by the formation of Lewy bodies made primarily of the α-synuclein protein encoded by the synuclein alpha (SNCA) gene. We hypothesize that COVID-19 may modulate PD progression through neuroinflammation induced by cytokine storms. This study aimed to elucidate the possible mechanisms and signaling pathways involved in COVID-19-triggered pathology associated with neurodegenerative diseases like PD. This study presents the analysis of the pathways involved in the downregulation of ACE2 following SARS-CoV-2 infection and its effect on PD progression. Through QIAGEN’s Ingenuity Pathway Analysis (IPA), the study identified the NISP as a top-five canonical pathway/signaling pathway and SNCA as a top-five upstream regulator. Core Analysis was also conducted on the associated molecules between COVID-19 and SNCA to construct a network connectivity map. The Molecule Activity Predictor tool was used to simulate the infection of SARS-CoV-2 by downregulating IFNG, which leads to the predicted activation of SNCA, and subsequently PD, through a dataset of intermediary molecules. Downstream effect analysis was further used to quantify the downregulation of ACE2 on SNCA activation.
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影响因子：
15.1
作者：
Campbell, Lee A.;Avdoshina, Valeriya;Rozzi, Summer;Mocchetti, Italo
通讯作者：
Mocchetti, Italo
影响因子：
4.3
作者：
Emamzadeh FN;Surguchov A
通讯作者：
Surguchov A
影响因子：
2.9
作者：
He, Y;Appel, S;Le, WD
通讯作者：
Le, WD
影响因子：
7.3
作者：
Ignatov, A.;Robert, J.;Schaller, H. C.
通讯作者：
Schaller, H. C.
影响因子：
5.3
作者：
Bruno, V;Battaglia, G;Flor, PJ
通讯作者：
Flor, PJ