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Neuropathophysiology of coronavirus disease 2019: neuroinflammation and blood brain barrier disruption are critical pathophysiological processes that contribute to the clinical symptoms of SARS-CoV-2 infection.
- Source :
-
Inflammopharmacology . Aug2021, Vol. 29 Issue 4, p939-963. 25p. - Publication Year :
- 2021
-
Abstract
- Coronavirus disease 2019 (COVID-19) is caused by the novel SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) first discovered in Wuhan, Hubei province, China in December 2019. SARS-CoV-2 has infected several millions of people, resulting in a huge socioeconomic cost and over 2.5 million deaths worldwide. Though the pathogenesis of COVID-19 is not fully understood, data have consistently shown that SARS-CoV-2 mainly affects the respiratory and gastrointestinal tracts. Nevertheless, accumulating evidence has implicated the central nervous system in the pathogenesis of SARS-CoV-2 infection. Unfortunately, however, the mechanisms of SARS-CoV-2 induced impairment of the central nervous system are not completely known. Here, we review the literature on possible neuropathogenic mechanisms of SARS-CoV-2 induced cerebral damage. The results suggest that downregulation of angiotensin converting enzyme 2 (ACE2) with increased activity of the transmembrane protease serine 2 (TMPRSS2) and cathepsin L in SARS-CoV-2 neuroinvasion may result in upregulation of proinflammatory mediators and reactive species that trigger neuroinflammatory response and blood brain barrier disruption. Furthermore, dysregulation of hormone and neurotransmitter signalling may constitute a fundamental mechanism involved in the neuropathogenic sequelae of SARS-CoV-2 infection. The viral RNA or antigenic peptides also activate or interact with molecular signalling pathways mediated by pattern recognition receptors (e.g., toll-like receptors), nuclear factor kappa B, Janus kinase/signal transducer and activator of transcription, complement cascades, and cell suicide molecules. Potential molecular targets and therapeutics of SARS-CoV-2 induced neurologic damage are also discussed. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 09254692
- Volume :
- 29
- Issue :
- 4
- Database :
- Academic Search Index
- Journal :
- Inflammopharmacology
- Publication Type :
- Academic Journal
- Accession number :
- 151526109
- Full Text :
- https://doi.org/10.1007/s10787-021-00806-x