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Potential Implications of Angiotensin-converting Enzyme 2 Blockades on Neuroinflammation in SARS-CoV-2 Infection

Rhian Thomas Orcid Logo, Deepraj Paul, Suresh Mohankumar Orcid Logo, Rhian Thomas, Chai Boon Kheng, Duraiswamy Basavan

Current Drug Targets, Volume: 22

Swansea University Authors: Rhian Thomas Orcid Logo, Suresh Mohankumar Orcid Logo, Rhian Thomas

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DOI (Published version): 10.2174/1389450122666211103165837

Abstract

Angiotensin-converting enzyme 2 (ACE2) has been reported as a portal for the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Consequently, scientific strategies to combat coronavirus disease of 2019 (COVID-19) were targeted to arrest SARS-CoV-2 invasion by blocking ACE2. Whil...

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Published in: Current Drug Targets
ISSN: 1389-4501 1873-5592
Published: Bentham Science Publishers Ltd. 2021
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URI: https://cronfa.swan.ac.uk/Record/cronfa58742
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Consequently, scientific strategies to combat coronavirus disease of 2019 (COVID-19) were targeted to arrest SARS-CoV-2 invasion by blocking ACE2. While blocking ACE2 appears a beneficial approach to treat COVID-19, clinical concerns have been raised primarily due to the various intrinsic roles of ACE2 in neurological functions. Selective reports indicate that angiotensin receptor blockers (ARBs) and angiotensin-converting enzyme inhibitors (ACEIs) upregulate ACE2 levels. ACE2 metabolizes angiotensin II and several peptides, including apelin-13, neurotensin, kinetensin, dynorphin, [des-Arg9] bradykinin, and [Lys-des-Arg9]-bradykinin, which may elicit neuroprotective effects. Since ARBs and ACEIs upregulate ACE2, it may be hypothesized that patients with hypertension receiving ARBs and ACEIs may have higher expression of ACE2 and thus be at a greater risk of severe disease from the SARS-CoV-2 infections. However, recent clinical reports indicate the beneficial role of ARBs/ACEIs in reducing COVID-19 severity. Together, this warrants a further study of the effects of ACE2 blockades in hypertensive patients medicated with ARBs/ACEIs, and their consequential impact on neuronal health. However, the associations between their blockade and any neuroinflammation also warrant further research. This review collates mechanistic insights into the dichotomous roles of ACE2 in SARS-CoV-2 invasion and neurometabolic functions and the possible impact of ACE2 blockade on neuroinflammation. It has been concluded that ACE2 blockade imposes neuroinflammation. 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spelling 2022-01-27T13:51:08.6524873 v2 58742 2021-11-22 Potential Implications of Angiotensin-converting Enzyme 2 Blockades on Neuroinflammation in SARS-CoV-2 Infection 10f33f117e548cddfa6758ea130c3407 0000-0002-7286-2764 Rhian Thomas Rhian Thomas true false edce0da45e3933d3460963b966f4c84e 0000-0001-8862-2979 Suresh Mohankumar Suresh Mohankumar true false b11cc7b66e9276dd5c389996f26788b7 Rhian Thomas Rhian Thomas true false 2021-11-22 PHAR Angiotensin-converting enzyme 2 (ACE2) has been reported as a portal for the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Consequently, scientific strategies to combat coronavirus disease of 2019 (COVID-19) were targeted to arrest SARS-CoV-2 invasion by blocking ACE2. While blocking ACE2 appears a beneficial approach to treat COVID-19, clinical concerns have been raised primarily due to the various intrinsic roles of ACE2 in neurological functions. Selective reports indicate that angiotensin receptor blockers (ARBs) and angiotensin-converting enzyme inhibitors (ACEIs) upregulate ACE2 levels. ACE2 metabolizes angiotensin II and several peptides, including apelin-13, neurotensin, kinetensin, dynorphin, [des-Arg9] bradykinin, and [Lys-des-Arg9]-bradykinin, which may elicit neuroprotective effects. Since ARBs and ACEIs upregulate ACE2, it may be hypothesized that patients with hypertension receiving ARBs and ACEIs may have higher expression of ACE2 and thus be at a greater risk of severe disease from the SARS-CoV-2 infections. However, recent clinical reports indicate the beneficial role of ARBs/ACEIs in reducing COVID-19 severity. Together, this warrants a further study of the effects of ACE2 blockades in hypertensive patients medicated with ARBs/ACEIs, and their consequential impact on neuronal health. However, the associations between their blockade and any neuroinflammation also warrant further research. This review collates mechanistic insights into the dichotomous roles of ACE2 in SARS-CoV-2 invasion and neurometabolic functions and the possible impact of ACE2 blockade on neuroinflammation. It has been concluded that ACE2 blockade imposes neuroinflammation. [Abstract copyright: Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.] Journal Article Current Drug Targets 22 Bentham Science Publishers Ltd. 1389-4501 1873-5592 neuroinflammation, COVID-19, angiotensin-converting enzyme 2, hypertension, SARS-CoV-2 3 11 2021 2021-11-03 10.2174/1389450122666211103165837 COLLEGE NANME Pharmacy COLLEGE CODE PHAR Swansea University 2022-01-27T13:51:08.6524873 2021-11-22T13:21:08.3074541 Faculty of Medicine, Health and Life Sciences Swansea University Medical School - Medicine Rhian Thomas 0000-0002-7286-2764 1 Deepraj Paul 2 Suresh Mohankumar 0000-0001-8862-2979 3 Rhian Thomas 4 Chai Boon Kheng 5 Duraiswamy Basavan 6 58742__21737__66cb7dbeea094e1b97dea3d6399baffb.pdf 58742.pdf 2021-11-30T15:36:53.8010275 Output 480156 application/pdf Accepted Manuscript true 2022-11-03T00:00:00.0000000 true eng
title Potential Implications of Angiotensin-converting Enzyme 2 Blockades on Neuroinflammation in SARS-CoV-2 Infection
spellingShingle Potential Implications of Angiotensin-converting Enzyme 2 Blockades on Neuroinflammation in SARS-CoV-2 Infection
Rhian Thomas
Suresh Mohankumar
Rhian Thomas
title_short Potential Implications of Angiotensin-converting Enzyme 2 Blockades on Neuroinflammation in SARS-CoV-2 Infection
title_full Potential Implications of Angiotensin-converting Enzyme 2 Blockades on Neuroinflammation in SARS-CoV-2 Infection
title_fullStr Potential Implications of Angiotensin-converting Enzyme 2 Blockades on Neuroinflammation in SARS-CoV-2 Infection
title_full_unstemmed Potential Implications of Angiotensin-converting Enzyme 2 Blockades on Neuroinflammation in SARS-CoV-2 Infection
title_sort Potential Implications of Angiotensin-converting Enzyme 2 Blockades on Neuroinflammation in SARS-CoV-2 Infection
author_id_str_mv 10f33f117e548cddfa6758ea130c3407
edce0da45e3933d3460963b966f4c84e
b11cc7b66e9276dd5c389996f26788b7
author_id_fullname_str_mv 10f33f117e548cddfa6758ea130c3407_***_Rhian Thomas
edce0da45e3933d3460963b966f4c84e_***_Suresh Mohankumar
b11cc7b66e9276dd5c389996f26788b7_***_Rhian Thomas
author Rhian Thomas
Suresh Mohankumar
Rhian Thomas
author2 Rhian Thomas
Deepraj Paul
Suresh Mohankumar
Rhian Thomas
Chai Boon Kheng
Duraiswamy Basavan
format Journal article
container_title Current Drug Targets
container_volume 22
publishDate 2021
institution Swansea University
issn 1389-4501
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publisher Bentham Science Publishers Ltd.
college_str Faculty of Medicine, Health and Life Sciences
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hierarchy_top_title Faculty of Medicine, Health and Life Sciences
hierarchy_parent_id facultyofmedicinehealthandlifesciences
hierarchy_parent_title Faculty of Medicine, Health and Life Sciences
department_str Swansea University Medical School - Medicine{{{_:::_}}}Faculty of Medicine, Health and Life Sciences{{{_:::_}}}Swansea University Medical School - Medicine
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description Angiotensin-converting enzyme 2 (ACE2) has been reported as a portal for the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Consequently, scientific strategies to combat coronavirus disease of 2019 (COVID-19) were targeted to arrest SARS-CoV-2 invasion by blocking ACE2. While blocking ACE2 appears a beneficial approach to treat COVID-19, clinical concerns have been raised primarily due to the various intrinsic roles of ACE2 in neurological functions. Selective reports indicate that angiotensin receptor blockers (ARBs) and angiotensin-converting enzyme inhibitors (ACEIs) upregulate ACE2 levels. ACE2 metabolizes angiotensin II and several peptides, including apelin-13, neurotensin, kinetensin, dynorphin, [des-Arg9] bradykinin, and [Lys-des-Arg9]-bradykinin, which may elicit neuroprotective effects. Since ARBs and ACEIs upregulate ACE2, it may be hypothesized that patients with hypertension receiving ARBs and ACEIs may have higher expression of ACE2 and thus be at a greater risk of severe disease from the SARS-CoV-2 infections. However, recent clinical reports indicate the beneficial role of ARBs/ACEIs in reducing COVID-19 severity. Together, this warrants a further study of the effects of ACE2 blockades in hypertensive patients medicated with ARBs/ACEIs, and their consequential impact on neuronal health. However, the associations between their blockade and any neuroinflammation also warrant further research. This review collates mechanistic insights into the dichotomous roles of ACE2 in SARS-CoV-2 invasion and neurometabolic functions and the possible impact of ACE2 blockade on neuroinflammation. It has been concluded that ACE2 blockade imposes neuroinflammation. [Abstract copyright: Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.]
published_date 2021-11-03T04:15:31Z
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