SARS-CoV-2 signaling and interactions with stimulant drugs of abuse via Sigma-1R: Impact on the BBB
SARS-CoV-2 signaling and interactions with stimulant drugs of abuse via Sigma-1R: Impact on the BBB
批准号:
10646325
负责人:
Gabriela Cristina Brailoiu
金额:
$47.63万
依托单位国家:
美国
项目类别:
财政年份:
2022
资助国家:
美国
项目状态:
未结题
起止时间:
2022-07-01 至 2027-04-30
关键词:
2019-nCoVACE2AcuteAdherens JunctionAffectBinding ProteinsBiological ModelsBlood - brain barrier anatomyCOVID-19COVID-19 pandemicCOVID-19 patientCalciumCalcium SignalingCell surfaceCellsCellular StressCentral Nervous SystemCerebrovascular systemChronicClinicalCocaineContractsCytoskeletonDataDependenceElementsEndothelial CellsEventGeneticHealthHomeostasisHomologous GeneImpairmentIn VitroInfectionInvestigationJupiterKnowledgeLungMicrobeMicroscopyMicrotubulesMitochondriaMolecular ChaperonesNAADPNeurologic SymptomsOrganPathway interactionsPermeabilityPersonsProcessProteinsRattusReactive Oxygen SpeciesReportingResearchRoleSARS coronavirusSARS-CoV-2 exposureSARS-CoV-2 infectionSARS-CoV-2 spike proteinSecond Messenger SystemsSignal TransductionSignaling ProteinStimulantStructureTestingTight JunctionsToxinVascular Endothelial CellViralViral ProteinsVirusantagonistblood damageblood-brain barrier disruptionblood-brain barrier functionblood-brain barrier permeabilizationbody systembrain endothelial cellbrain tissuecapsulecentral nervous system injurycocaine exposurecoronavirus diseasedrug of abuseelectric impedancein vitro Modelin vivoinsightnovel therapeutic interventionpathogenpharmacologicpsychostimulantreal time monitoringreceptorsigma-1 receptorstimulant use disordertrafficking
中文摘要
导致COVID-10的病毒SARS-CoV-2会产生影响
英文摘要
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.
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