Meta-Analysis of APP Expression Modulated by SARS-CoV-2 Infection via the ACE2 Receptor.
Meta-Analysis of APP Expression Modulated by SARS-CoV-2 Infection via the ACE2 Receptor.
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DOI：
10.3390/ijms23031182
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发表时间：
2022-01-21
影响因子：
5.6
通讯作者：
Chang SL
中科院分区：
文献类型：
--
作者：
Caradonna A;Patel T;Toleska M;Alabed S;Chang SL
阿尔茨海默病（AD）的特征在于淀粉样蛋白β前体蛋白（APP）的不适当裂解导致淀粉样蛋白β（Aβ）斑块的沉积。在对2019冠状病毒（COVID-19）感染引起的炎症进行研究之后，本研究调查了COVID-19对APP表达的影响。利用QIAGEN Influencity Pathway Analysis（IPA）进行了一项荟萃分析，以检查严重急性呼吸综合征-冠状病毒-2（SARS-CoV-2）与病毒结合血管紧张素转换酶-2（ACE 2）受体后APP表达的调节之间的联系。对严重急性呼吸综合征（SARS）冠状病毒节点的感染进行了核心分析，其中包括受SARS-CoV-2影响的分子，揭示了其上游调控因子。在上游调节子和ACE 2之间以及ACE 2和APP之间发现了中间分子。上游调节子的激活下调ACE 2的表达，Z评分为-1.719（p值= 0.086）和上调APP，Z评分为1.898（p值= 0.058），显示结果偶然发生的几率小于10%，并表明ACE 2和APP表达之间存在反比关系。神经炎症信号通路是参与APP上调的第五大经典通路。研究结果表明，SARS-CoV-2可下调ACE 2，导致APP上调，并可能加剧AD的发病和进展。
Alzheimer’s disease (AD) is characterized by the deposition of amyloid-beta (Aβ) plaques from improper amyloid-beta precursor protein (APP) cleavage. Following studies of inflammation caused by coronavirus-2019 (COVID-19) infection, this study investigated the impact of COVID-19 on APP expression. A meta-analysis was conducted utilizing QIAGEN Ingenuity Pathway Analysis (IPA) to examine the link between severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) and the modulation of APP expression upon virus binding the Angiotensin-converting enzyme-2 (ACE2) receptor. A Core Analysis was run on the infection by severe acute respiratory syndrome (SARS) coronavirus node, which included molecules affected by SARS-CoV-2, revealing its upstream regulators. Intermediary molecules were found between the upstream regulators and ACE2 and between ACE2 and APP. Activation of the upstream regulators downregulated the expression of ACE2 with a Z-score of −1.719 (p-value = 0.086) and upregulated APP with a Z-score of 1.898 (p-value = 0.058), showing a less than 10% chance of the results occurring by chance and pointing to an inverse relationship between ACE2 and APP expression. The neuroinflammation signaling pathway was the fifth top canonical pathway involved in APP upregulation. The study results suggest that ACE2 could be downregulated by SARS-CoV-2, resulting in APP upregulation, and potentially exacerbating the onset and progression of AD.
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DOI：
10.1007/s10096-020-04138-6
发表时间：
2021-05
期刊：
European journal of clinical microbiology & infectious diseases : official publication of the European Society of Clinical Microbiology
影响因子：
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作者：
Beyerstedt S;Casaro EB;Rangel ÉB
通讯作者：
Rangel ÉB
DOI：
10.1186/s13195-020-00744-w
发表时间：
2020-12-30
期刊：
Alzheimer's research & therapy
影响因子：
--
作者：
Miners S;Kehoe PG;Love S
通讯作者：
Love S
DOI：
10.1186/s13195-016-0217-7
发表时间：
2016-11-25
期刊：
Alzheimer's research & therapy
影响因子：
--
作者：
Kehoe PG;Wong S;Al Mulhim N;Palmer LE;Miners JS
通讯作者：
Miners JS
DOI：
10.3390/healthcare8030286
发表时间：
2020-08-21
期刊：
Healthcare (Basel, Switzerland)
影响因子：
--
作者：
Abate G;Memo M;Uberti D
通讯作者：
Uberti D
影响因子：
5.4
作者：
Glowacka, Ilona;Bertram, Stephanie;Poehlmann, Stefan
通讯作者：
Poehlmann, Stefan