Shared Mechanisms of Blood-Brain Barrier Dysfunction and Neuroinflammation in Coronavirus Disease 2019 and Alzheimer Disease.

IF 4.7 2区 医学 Q1 PATHOLOGY
Meredith G Mayer, Tracy Fischer
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引用次数: 0

Abstract

The coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has highlighted the virus's impact on the central nervous system and its potential to exacerbate neurodegenerative diseases, like Alzheimer disease (AD). Emerging evidence suggests that SARS-CoV-2 infection contributes to chronic neuroinflammation, a key driver in the etiopathogenesis of AD. Shared mechanisms, including blood-brain barrier (BBB) dysfunction, systemic inflammation, and activation of immune pathways, may link SARS-CoV-2 infection to AD onset and/or progression, particularly among vulnerable individuals, such as those of advanced age. This review explores convergent pathways involving the renin-angiotensin-aldosterone system, Wnt/β-catenin signaling, NF-κB activation, and interferon signaling, focusing on their roles in BBB integrity and neuroinflammation. SARS-CoV-2-mediated angiotensin-converting enzyme 2 depletion disrupts renin-angiotensin-aldosterone system homeostasis, favoring proinflammatory signaling that parallels vascular dysfunction in AD. Dysregulation of Wnt/β-catenin signaling exacerbates BBB permeability, whereas NF-κB and interferon pathways contribute to BBB breakdown and propagate central nervous system inflammation via endothelial and immune cell activation. These interactions may amplify prodromal AD pathology and/or initiate AD pathogenesis. By identifying mechanistic overlaps between COVID-19 and AD, this review underlines the need for therapeutic strategies targeting shared pathways of inflammation and BBB dysfunction. Understanding these connections is critical for mitigating the long-term neurologic sequelae of COVID-19 and reducing the burden of AD.

2019冠状病毒病和阿尔茨海默病中血脑屏障功能障碍和神经炎症的共同机制
由严重急性呼吸综合征冠状病毒2 (SARS-CoV-2)引起的2019年冠状病毒病(COVID-19)大流行突显了该病毒对中枢神经系统的影响及其加剧阿尔茨海默病(AD)等神经退行性疾病的潜力。新证据表明,SARS-CoV-2感染可导致慢性神经炎症,这是阿尔茨海默病发病的关键驱动因素。包括血脑屏障(BBB)功能障碍、全身性炎症和免疫途径激活在内的共同机制可能将SARS-CoV-2感染与阿尔茨海默病的发病和/或进展联系起来,特别是在老年人等易感人群中。这篇综述探讨了包括肾素-血管紧张素-醛固酮系统、Wnt/β-catenin信号、NF-κB激活和干扰素信号在内的趋同通路,重点讨论了它们在血脑屏障完整性和神经炎症中的作用。sars - cov -2介导的血管紧张素转换酶2耗竭破坏肾素-血管紧张素-醛固酮系统的稳态,有利于AD中与血管功能障碍相似的促炎信号。Wnt/β-catenin信号的失调加剧了血脑屏障的通透性,而NF-κB和干扰素通路通过内皮细胞和免疫细胞激活促进血脑屏障的破坏和传播中枢神经系统炎症。这些相互作用可能会放大AD前驱病理和/或启动AD发病机制。通过确定COVID-19和AD之间的机制重叠,本综述强调了针对炎症和血脑屏障功能障碍共享途径的治疗策略的必要性。了解这些联系对于减轻COVID-19的长期神经系统后遗症和减轻阿尔茨海默病的负担至关重要。
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来源期刊
CiteScore
11.40
自引率
0.00%
发文量
178
审稿时长
30 days
期刊介绍: The American Journal of Pathology, official journal of the American Society for Investigative Pathology, published by Elsevier, Inc., seeks high-quality original research reports, reviews, and commentaries related to the molecular and cellular basis of disease. The editors will consider basic, translational, and clinical investigations that directly address mechanisms of pathogenesis or provide a foundation for future mechanistic inquiries. Examples of such foundational investigations include data mining, identification of biomarkers, molecular pathology, and discovery research. Foundational studies that incorporate deep learning and artificial intelligence are also welcome. High priority is given to studies of human disease and relevant experimental models using molecular, cellular, and organismal approaches.
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