Lim Key-Hwan, Yang Sumin, Kim Sung-Hyun, Joo Jae-Yeol
Neurodegenerative Disease Research Group, Korea Brain Research Institute, Daegu, South Korea.
Front Genet. 2021 Oct 21;12:741175. doi: 10.3389/fgene.2021.741175. eCollection 2021.
Recent preclinical studies show that Neuropilin-1 (NRP1), which is a transmembrane protein with roles in neuronal development, axonal outgrowth, and angiogenesis, also plays a role in the infectivity of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Thus, we hypothesize that NRP1 may be upregulated in Alzheimer's disease (AD) patients and that a correlation between AD and SARS-CoV-2 NRP1-mediated infectivity may exist as angiotensin converting enzyme 2 (ACE2). We used an AD mouse model that mimics AD and performed high-throughput total RNA-seq with brain tissue and whole blood. For quantification of NRP1 in AD, brain tissues and blood were subjected to Western blotting and real-time quantitative PCR (RT-qPCR) analysis. analysis for NRP1 expression in AD patients has been performed on human hippocampus data sets. Many cases of severe symptoms of COVID-19 are concentrated in an elderly group with complications such as diabetes, degenerative disease, and brain disorders. Total RNA-seq analysis showed that the gene was commonly overexpressed in the AD model. Similar to ACE2, the NRP1 protein is also strongly expressed in AD brain tissues. Interestingly, analysis revealed that the level of expression for NRP1 was distinct at age and AD progression. Given that NRP1 is highly expressed in AD, it is important to understand and predict that NRP1 may be a risk factor for SARS-CoV-2 infection in AD patients. This supports the development of potential therapeutic drugs to reduce SARS-CoV-2 transmission.
最近的临床前研究表明,神经纤毛蛋白-1(NRP1)作为一种在神经元发育、轴突生长和血管生成中起作用的跨膜蛋白,在严重急性呼吸综合征冠状病毒2(SARS-CoV-2)的感染性方面也发挥作用。因此,我们假设NRP1可能在阿尔茨海默病(AD)患者中上调,并且AD与SARS-CoV-2 NRP1介导的感染性之间可能存在关联,就如同血管紧张素转换酶2(ACE2)一样。我们使用了一种模拟AD的AD小鼠模型,并对脑组织和全血进行了高通量总RNA测序。为了定量AD中的NRP1,对脑组织和血液进行了蛋白质免疫印迹和实时定量PCR(RT-qPCR)分析。已经对人类海马体数据集进行了AD患者中NRP1表达的分析。许多新冠肺炎严重症状的病例集中在患有糖尿病、退行性疾病和脑部疾病等并发症的老年人群体中。总RNA测序分析表明,该基因在AD模型中普遍过表达。与ACE2类似,NRP1蛋白在AD脑组织中也强烈表达。有趣的是,分析显示NRP1的表达水平在年龄和AD进展过程中有所不同。鉴于NRP1在AD中高度表达,了解并预测NRP1可能是AD患者感染SARS-CoV-2的一个风险因素非常重要。这支持了开发潜在治疗药物以减少SARS-CoV-2传播。