Vascular Endothelial Growth Factor (VEGF) as a Vital Target for Brain Inflammation during the COVID-19 Outbreak

Yin, Xi Xi; Zheng, Xiang Rong; Wang, Peng; Wu, Mao Lan; Mao, Xiao

doi:10.1021/acschemneuro.0c00294

Cited by 73 publications

(71 citation statements)

References 6 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Finally, increasing VEGF concentrations, which recruit inflammatory cells into the brain and sustain neuroinflammation, have been named as target for COVID-19 treatment [167]. The COVID-19 entry receptor ACE2 activates RAAS for neuroinflammation and VEGF synthesis by Ang II binding to AT 1 R (reviewed in ref.…”

Section: Neuropsychiatry and Neurodegenerative Disorders Associated Tmentioning

confidence: 99%

See 1 more Smart Citation

Hyperactivation of P2X7 receptors as a culprit of COVID-19 neuropathology

et al. 2020

View full text Add to dashboard Cite

Scientists and health professionals are exhaustively trying to contain the coronavirus disease 2019 (COVID-19) pandemic by elucidating viral invasion mechanisms, possible drugs to prevent viral infection/replication, and health cares to minimize individual exposure. Although neurological symptoms are being reported worldwide, neural acute and long-term consequences of SARS-CoV-2 are still unknown. COVID-19 complications are associated with exacerbated immunoinflammatory responses to SARS-CoV-2 invasion. In this scenario, pro-inflammatory factors are intensely released into the bloodstream, causing the so-called “cytokine storm”. Both pro-inflammatory factors and viruses may cross the blood–brain barrier and enter the central nervous system, activating neuroinflammatory responses accompanied by hemorrhagic lesions and neuronal impairment, which are largely described processes in psychiatric disorders and neurodegenerative diseases. Therefore, SARS-CoV-2 infection could trigger and/or worse brain diseases. Moreover, patients with central nervous system disorders associated to neuroimmune activation (e.g. depression, Parkinson’s and Alzheimer’s disease) may present increased susceptibility to SARS-CoV-2 infection and/or achieve severe conditions. Elevated levels of extracellular ATP induced by SARS-CoV-2 infection may trigger hyperactivation of P2X7 receptors leading to NLRP3 inflammasome stimulation as a key mediator of neuroinvasion and consequent neuroinflammatory processes, as observed in psychiatric disorders and neurodegenerative diseases. In this context, P2X7 receptor antagonism could be a promising strategy to prevent or treat neurological complications in COVID-19 patients.

show abstract

Section: Neuropsychiatry and Neurodegenerative Disorders Associated Tmentioning

confidence: 99%

“…The COVID-19 entry receptor ACE2 activates RAAS for neuroinflammation and VEGF synthesis by Ang II binding to AT 1 R (reviewed in ref. [167]). Besides ACE2, aberrant P2X7 receptor activation also induces VEGF release and signaling in the brain [168].…”

Section: Neuropsychiatry and Neurodegenerative Disorders Associated Tmentioning

confidence: 99%

Hyperactivation of P2X7 receptors as a culprit of COVID-19 neuropathology

et al. 2020

View full text Add to dashboard Cite

show abstract

“…As ACE2 is widely expressed on the epithelial cells of the oral mucosa, SARS‐CoV‐2 can breach the BNB accessing the CNS via the cranial nerve using axonal transport machinery (Zhou et al., 2020). The upregulated vascular endothelial growth factor VEGF (C and A) is associated with COVID‐19 endothelial barrier dysfunction (Ackermann et al., 2020; Yin et al., 2020), and specifically with the BNB (Lim et al., 2014). As VEGF is also related to angiopoietins (Ang I and Ang II), accumulation of Ang II facilitates the elevation of VEGF and inversely augments Ang II, which forms a vicious cycle in the release of inflammatory cytokines including TNF‐α, IL‐1β, IL‐6, IL‐8, and ICAM‐1, which causes BBB and BNSB disruption (Yin et al., 2020).…”

Section: Blood–nervous System Barriers (Bnsbs)mentioning

confidence: 99%

Severe acute respiratory syndrome coronavirus 2 infection reaches the human nervous system: How?

Uversky

Elrashdy

Aljadawi

et al. 2020

J of Neuroscience Research

View full text Add to dashboard Cite

Without protective and/or therapeutic agents the severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infection known as coronavirus disease 2019 is quickly spreading worldwide. It has surprising transmissibility potential, since it could infect all ages, gender, and human sectors. It attacks respiratory, gastrointestinal, urinary, hepatic, and endovascular systems and can reach the peripheral nervous system (PNS) and central nervous system (CNS) through known and unknown mechanisms. The reports on the neurological manifestations and complications of the SARS‐CoV‐2 infection are increasing exponentially. Herein, we enumerate seven candidate routes, which the mature or immature SARS‐CoV‐2 components could use to reach the CNS and PNS, utilizing the within‐body cross talk between organs. The majority of SARS‐CoV‐2–infected patients suffer from some neurological manifestations (e.g., confusion, anosmia, and ageusia). It seems that although the mature virus did not reach the CNS or PNS of the majority of patients, its unassembled components and/or the accompanying immune‐mediated responses may be responsible for the observed neurological symptoms. The viral particles and/or its components have been specifically documented in endothelial cells of lung, kidney, skin, and CNS. This means that the blood–endothelial barrier may be considered as the main route for SARS‐CoV‐2 entry into the nervous system, with the barrier disruption being more logical than barrier permeability, as evidenced by postmortem analyses.

show abstract

“…Numerous studies have confirmed a key role of VEGF-A as potential therapeutic target in ALI and ARDS due do the increased vascular permeability and pulmonary edema [258]. Furthermore, VEGF-A has been involved in disruption of the blood-brain barrier and may contribute to brain inflammation in the course of SARS-CoV-2 infection [259]. Thus, blockage of VEGF-A might have a role in COVID-19 management.…”

Section: Anti-vascular Endothelial Growth Factor-a (Vegf-a) Mabmentioning

confidence: 98%

Approaching coronavirus disease 2019: Mechanisms of action of repurposed drugs with potential activity against SARS-CoV-2

Lisi¹,

Lacal

Barbaccia

et al. 2020

Biochemical Pharmacology

View full text Add to dashboard Cite

On March 11, 2020, the World Health Organization (WHO) declared the severe acute respiratory syndrome caused by coronavirus 2 (SARS-CoV-2) a global pandemic. As of July 2020, SARS-CoV-2 has infected more than 14 million people and provoked more than 590,000 deaths, worldwide. From the beginning, a variety of pharmacological treatments has been empirically used to cope with the life-threatening complications associated with Corona Virus Disease 2019 (COVID-19). Thus far, only a couple of them and not consistently across reports have been shown to further decrease mortality, respect to what can be achieved with supportive care. In most cases, and due to the urgency imposed by the number and severity of the patients' clinical conditions, the choice of treatment has been limited to repurposed drugs, approved for other indications, or investigational agents used for other viral infections often rendered available on a compassionate-use basis. The rationale for drug selection was mainly, though not exclusively, based either i) on the activity against other coronaviruses or RNA viruses in order to potentially hamper viral entry and replication in the epithelial cells of the airways, and/or ii) on the ability to modulate the excessive inflammatory reaction deriving from dysregulated host immune responses against the SARS-CoV-2. In several months, an exceptionally large number of clinical trials have been designed to evaluate the safety and efficacy of anti-COVID-19 therapies in different clinical settings (treatment or pre-and post-exposure prophylaxis) and levels of disease severity, but only few of them have been completed so far. This review focuses on the molecular mechanisms of action that have provided the scientific rationale for the empirical use and evaluation in clinical trials of structurally different and often functionally unrelated drugs during the SARS-CoV-2 pandemic.

show abstract

Vascular Endothelial Growth Factor (VEGF) as a Vital Target for Brain Inflammation during the COVID-19 Outbreak

Cited by 73 publications

References 6 publications

Hyperactivation of P2X7 receptors as a culprit of COVID-19 neuropathology

Hyperactivation of P2X7 receptors as a culprit of COVID-19 neuropathology

Severe acute respiratory syndrome coronavirus 2 infection reaches the human nervous system: How?

Approaching coronavirus disease 2019: Mechanisms of action of repurposed drugs with potential activity against SARS-CoV-2

Contact Info

Product

Resources

About