Abstract
Angiotensin-converting enzyme 2 (ACE2), a key enzyme in the renin-angiotensin system (RAS), is expressed in various tissues and organs, including the central nervous system (CNS). The spike protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus responsible for coronavirus disease-2019 (COVID-19), binds to ACE2, which raises concerns about the potential for viral infection in the CNS. There are numerous reports suggesting a link between SARS-CoV-2 infection and neurological manifestations. This study aimed to present an updated review of the role of brain RAS components, especially ACE2, in neurological complications induced by SARS-CoV-2 infection. Several routes of SARS-CoV-2 entry into the brain have been proposed. Because an anosmia condition appeared broadly in COVID-19 patients, the olfactory nerve route was suggested as an early pathway for SARS-CoV-2 entry into the brain. In addition, a hematogenous route via disintegrations in the blood-brain barrier following an increase in systemic cytokine and chemokine levels and retrograde axonal transport, especially via the vagus nerve innervating lungs, have been described. Common nonspecific neurological symptoms in COVID-19 patients are myalgia, headache, anosmia, and dysgeusia. However, more severe outcomes include cerebrovascular diseases, cognitive impairment, anxiety, encephalopathy, and stroke. Alterations in brain RAS components such as angiotensin II (Ang II) and ACE2 mediate neurological manifestations of SARS-CoV-2 infection, at least in part. Downregulation of ACE2 due to SARS-CoV-2 infection, followed by an increase in Ang II levels, leads to hyperinflammation and oxidative stress, which in turn accelerates neurodegeneration in the brain. Furthermore, ACE2 downregulation in the hypothalamus induces stress and anxiety responses by increasing corticotropin-releasing hormone. SARS-CoV-2 infection may also dysregulate the CNS neurotransmission, leading to neurological complications observed in severe cases of COVID-19. It can be concluded that the neurological manifestations of COVID-19 may be partially associated with changes in brain RAS components.
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.