Sfera Adonis, Osorio Carolina, Rahman Leah, Zapata-Martín Del Campo Carlos Manuel, Maldonado Jose Campo, Jafri Nyla, Cummings Michael Allen, Maurer Steve, Kozlakidis Zisis
Department of Psychiatry, Loma Linda University, Loma Linda, CA, United States.
Patton State Hospital, San Bernardino, CA, United States.
Front Cell Neurosci. 2021 Oct 29;15:770387. doi: 10.3389/fncel.2021.770387. eCollection 2021.
SARS-CoV-2 virus, the etiologic agent of COVID-19, has affected almost every aspect of human life, precipitating stress-related pathology in vulnerable individuals. As the prevalence rate of posttraumatic stress disorder in pandemic survivors exceeds that of the general and special populations, the virus may predispose to this disorder by directly interfering with the stress-processing pathways. The SARS-CoV-2 interactome has identified several antigens that may disrupt the blood-brain-barrier by inducing premature senescence in many cell types, including the cerebral endothelial cells. This enables the stress molecules, including angiotensin II, endothelin-1 and plasminogen activator inhibitor 1, to aberrantly activate the amygdala, hippocampus, and medial prefrontal cortex, increasing the vulnerability to stress related disorders. This is supported by observing the beneficial effects of angiotensin receptor blockers and angiotensin converting enzyme inhibitors in both posttraumatic stress disorder and SARS-CoV-2 critical illness. In this narrative review, we take a closer look at the virus-host dialog and its impact on the renin-angiotensin system, mitochondrial fitness, and brain-derived neurotrophic factor. We discuss the role of furin cleaving site, the fibrinolytic system, and Sigma-1 receptor in the pathogenesis of psychological trauma. In other words, learning from the virus, clarify the molecular underpinnings of stress related disorders, and design better therapies for these conditions. In this context, we emphasize new potential treatments, including furin and bromodomains inhibitors.
严重急性呼吸综合征冠状病毒2（SARS-CoV-2）是冠状病毒病（COVID-19）的病原体，几乎影响了人类生活的方方面面，在易感个体中引发了与应激相关的病理状况。由于大流行幸存者中创伤后应激障碍的患病率超过了普通人群和特殊人群，该病毒可能通过直接干扰应激处理途径而使人易患这种疾病。SARS-CoV-2相互作用组已鉴定出几种抗原，这些抗原可能通过在包括脑内皮细胞在内的多种细胞类型中诱导早衰来破坏血脑屏障。这使得包括血管紧张素II、内皮素-1和纤溶酶原激活物抑制剂1在内的应激分子异常激活杏仁核、海马体和内侧前额叶皮层，增加了患应激相关疾病的易感性。血管紧张素受体阻滞剂和血管紧张素转换酶抑制剂在创伤后应激障碍和SARS-CoV-2危重症中均具有有益作用，这一现象支持了上述观点。在这篇叙述性综述中，我们更深入地探讨病毒与宿主的相互作用及其对肾素-血管紧张素系统、线粒体健康和脑源性神经营养因子的影响。我们讨论了弗林蛋白酶切割位点、纤维蛋白溶解系统和西格玛-1受体在心理创伤发病机制中的作用。换句话说，从病毒中学习，阐明应激相关疾病的分子基础，并为这些疾病设计更好的治疗方法。在此背景下，我们强调了新的潜在治疗方法，包括弗林蛋白酶和溴结构域抑制剂。
