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.

SARS-COV-2（导致Covid-10的病毒）影响多个器官系统，包括中枢神经系统。大约在在脑组织中发现了三分之一的Covid-19患者和病毒。 SARS-COV-2使用血管紧张素转化位于细胞表面上的酶2（ACE2）进入细胞，而尖峰病毒的蛋白质是ACE2的关键识别元件。 ACE2由内皮细胞表达构成血脑屏障（BBB）的大脑脉管系统，主要进入的主要障碍病原体和毒素进入中枢神经系统。最近，已显示SARS-COV-2峰值蛋白可以改变BBB 使用体外模型系统的功能。许多滥用药物，包括精神刺激剂，负面影响BBB功能。因此，在存在的情况下，SARS-COV-E感染很可能精神刺激剂可能会导致BBB造成更大的损害，从而进一步增加屏障的渗透性和导致中枢神经系统受伤。因此，研究Sarscov-相互作用的机制 2需要BBB上的兴奋剂。