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ACE2, Circumventricular Organs and the Hypothalamus, and COVID-19

The SARS-CoV-2 virus gains entry to cells by binding to angiotensin-converting enzyme 2 (ACE2). Since circumventricular organs and parts of the hypothalamus lack a blood–brain barrier, and immunohistochemical studies demonstrate that ACE2 is highly expressed in circumventricular organs which are int...

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Autores principales: Ong, Wei-Yi, Satish, R. L., Herr, Deron R.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer US 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9023728/
https://www.ncbi.nlm.nih.gov/pubmed/35451691
http://dx.doi.org/10.1007/s12017-022-08706-1
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author Ong, Wei-Yi
Satish, R. L.
Herr, Deron R.
author_facet Ong, Wei-Yi
Satish, R. L.
Herr, Deron R.
author_sort Ong, Wei-Yi
collection PubMed
description The SARS-CoV-2 virus gains entry to cells by binding to angiotensin-converting enzyme 2 (ACE2). Since circumventricular organs and parts of the hypothalamus lack a blood–brain barrier, and immunohistochemical studies demonstrate that ACE2 is highly expressed in circumventricular organs which are intimately connected to the hypothalamus, and the hypothalamus itself, these might be easy entry points for SARS-CoV-2 into the brain via the circulation. High ACE2 protein expression is found in the subfornical organ, area postrema, and the paraventricular nucleus of the hypothalamus (PVH). The subfornical organ and PVH are parts of a circuit to regulate osmolarity in the blood, through the secretion of anti-diuretic hormone into the posterior pituitary. The PVH is also the stress response centre in the brain. It controls not only pre-ganglionic sympathetic neurons, but is also a source of corticotropin-releasing hormone, that induces the secretion of adrenocorticotropic hormone from the anterior pituitary. It is proposed that the function of ACE2 in the circumventricular organs and the PVH could be diminished by binding with SARS-CoV-2, thus leading to a reduction in the ACE2/Ang (1–7)/Mas receptor (MasR) signalling axis, that modulates ACE/Ang II/AT1R signalling. This could result in increased presympathetic activity/neuroendocrine secretion from the PVH, and effects on the hypothalamic–pituitary–adrenal axis activity. Besides the bloodstream, the hypothalamus might also be affected by SARS-CoV-2 via transneuronal spread along the olfactory/limbic pathways. Exploring potential therapeutic pathways to prevent or attenuate neurological symptoms of COVID-19, including drugs which modulate ACE signalling, remains an important area of unmet medical need.
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spelling pubmed-90237282022-04-22 ACE2, Circumventricular Organs and the Hypothalamus, and COVID-19 Ong, Wei-Yi Satish, R. L. Herr, Deron R. Neuromolecular Med Review The SARS-CoV-2 virus gains entry to cells by binding to angiotensin-converting enzyme 2 (ACE2). Since circumventricular organs and parts of the hypothalamus lack a blood–brain barrier, and immunohistochemical studies demonstrate that ACE2 is highly expressed in circumventricular organs which are intimately connected to the hypothalamus, and the hypothalamus itself, these might be easy entry points for SARS-CoV-2 into the brain via the circulation. High ACE2 protein expression is found in the subfornical organ, area postrema, and the paraventricular nucleus of the hypothalamus (PVH). The subfornical organ and PVH are parts of a circuit to regulate osmolarity in the blood, through the secretion of anti-diuretic hormone into the posterior pituitary. The PVH is also the stress response centre in the brain. It controls not only pre-ganglionic sympathetic neurons, but is also a source of corticotropin-releasing hormone, that induces the secretion of adrenocorticotropic hormone from the anterior pituitary. It is proposed that the function of ACE2 in the circumventricular organs and the PVH could be diminished by binding with SARS-CoV-2, thus leading to a reduction in the ACE2/Ang (1–7)/Mas receptor (MasR) signalling axis, that modulates ACE/Ang II/AT1R signalling. This could result in increased presympathetic activity/neuroendocrine secretion from the PVH, and effects on the hypothalamic–pituitary–adrenal axis activity. Besides the bloodstream, the hypothalamus might also be affected by SARS-CoV-2 via transneuronal spread along the olfactory/limbic pathways. Exploring potential therapeutic pathways to prevent or attenuate neurological symptoms of COVID-19, including drugs which modulate ACE signalling, remains an important area of unmet medical need. Springer US 2022-04-22 2022 /pmc/articles/PMC9023728/ /pubmed/35451691 http://dx.doi.org/10.1007/s12017-022-08706-1 Text en © The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature 2022 This article is made available via the PMC Open Access Subset for unrestricted research re-use and secondary analysis in any form or by any means with acknowledgement of the original source. These permissions are granted for the duration of the World Health Organization (WHO) declaration of COVID-19 as a global pandemic.
spellingShingle Review
Ong, Wei-Yi
Satish, R. L.
Herr, Deron R.
ACE2, Circumventricular Organs and the Hypothalamus, and COVID-19
title ACE2, Circumventricular Organs and the Hypothalamus, and COVID-19
title_full ACE2, Circumventricular Organs and the Hypothalamus, and COVID-19
title_fullStr ACE2, Circumventricular Organs and the Hypothalamus, and COVID-19
title_full_unstemmed ACE2, Circumventricular Organs and the Hypothalamus, and COVID-19
title_short ACE2, Circumventricular Organs and the Hypothalamus, and COVID-19
title_sort ace2, circumventricular organs and the hypothalamus, and covid-19
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9023728/
https://www.ncbi.nlm.nih.gov/pubmed/35451691
http://dx.doi.org/10.1007/s12017-022-08706-1
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