SARS-CoV-2 signaling and interactions with stimulant drugs of abuse via Sigma-1R: Impact on the BBB

SARS-CoV-2 信号传导以及通过 Sigma-1R 与滥用兴奋剂药物的相互作用：对 BBB 的影响

基本信息

批准号：
10646325
负责人：
Gabriela Cristina Brailoiu
金额：
$ 47.63万
依托单位：
TEMPLE UNIV OF THE COMMONWEALTH
依托单位国家：
美国
项目类别：
财政年份：
2022
资助国家：
美国
起止时间：
2022-07-01 至 2027-04-30
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10646325
关键词：
2019-nCoV ACE2 Acute Adherens Junction Affect Binding Proteins Biological Models Blood - brain barrier anatomy COVID-19 COVID-19 pandemic COVID-19 patient Calcium Calcium Signaling Cell surface Cells Cellular Stress Central Nervous System Cerebrovascular system Chronic Clinical Cocaine Contracts Cytoskeleton Data Dependence Elements Endothelial Cells Event Genetic Health Homeostasis Homologous Gene Impairment In Vitro Infection Investigation Jupiter Knowledge Lung Microbe Microscopy Microtubules Mitochondria Molecular Chaperones NAADP Neurologic Symptoms Organ Pathway interactions Permeability Persons Process Proteins Rattus Reactive Oxygen Species Reporting Research Role SARS coronavirus SARS-CoV-2 exposure SARS-CoV-2 infection SARS-CoV-2 spike protein Second Messenger Systems Signal Transduction Signaling Protein Stimulant Structure Testing Tight Junctions Toxin Vascular Endothelial Cell Viral Viral Proteins Virus antagonist blood damage blood-brain barrier disruption blood-brain barrier function blood-brain barrier permeabilization body system brain endothelial cell brain tissue capsule central nervous system injury cocaine exposure coronavirus disease drug of abuse electric impedance in vitro Model in vivo insight novel therapeutic intervention pathogen pharmacologic psychostimulant real time monitoring receptor sigma-1 receptor stimulant use disorder trafficking

项目摘要

SARS-CoV-2, the virus that causes COVID-10, impacts multiple organ systems including the central nervous system. Neurological symptoms are seen in about one third of COVID-19 patients and the virus has been found in brain tissue. SARS-CoV-2 uses angiotensin converting enzyme 2 (ACE2) located on cell surfaces for entry into cells, and the spike protein of the virus is the key recognition element for ACE2. ACE2 is expressed by endothelial cells of the cerebral vasculature that comprise the blood-brain barrier (BBB), the main barrier to entry of pathogens and toxins into the CNS. Recently, SARS-CoV-2 spike protein has been shown to alter BBB function using in vitro model systems. Many drugs of abuse, including psychostimulants, negatively impact BBB function as well. Therefore, it is likely that SARS-CoV-e infection in the presence of psychostimulants could result in greater damage ot the BBB, further increasing barrier permeability and resulting in CNS injury. Thus, investigation of the mechanisms underlying the interactions of SARSCoV- 2 and stimulants on the BBB is needed.

引起 COVID-10 的病毒 SARS-CoV-2 会产生影响包括中枢神经系统在内的多个器官系统。神经系统症状见于约三分之一的 COVID-19 患者的脑组织中发现了病毒。 SARS-CoV-2 用途血管紧张素转换酶 2 (ACE2) 位于细胞表面，用于进入细胞，而尖峰病毒蛋白是ACE2的关键识别元件。 ACE2 由内皮细胞表达脑血管系统由血脑屏障 (BBB) 组成，是血液进入的主要屏障病原体和毒素进入中枢神经系统。最近，SARS-CoV-2 刺突蛋白已被证明可以改变 BBB 使用体外模型系统的功能。许多滥用药物，包括精神兴奋剂，都会产生负面影响也会影响 BBB 功能。因此，SARS-CoV-e 感染很可能是在存在以下物质的情况下发生的：精神兴奋剂可能对血脑屏障造成更大的损害，进一步增加屏障的通透性和导致中枢神经系统损伤。因此，研究 SARSCoV-2 相互作用的潜在机制 2、需要BBB兴奋剂。