====== Angiotensin-converting enzyme 2 receptor ======

Entry of [[SARS-CoV-2]] into human cells is dependent on the SARS-CoV receptor, angiotensin converting enzyme 2 ([[ACE]]2) receptor, and cathepsin. [[Cathepsin]] degrades the [[spike protein]] ([[S protein]]), which results in the entry of viral nucleic acid into the human host cell.

This [[receptor]] is also found in the [[CNS]] and plays a crucial role in autoregulating [[cerebral perfusion pressure]]
((Zhang H, Penninger JM, Li Y, Zhong N, Slutsky AS. Angiotensin-converting enzyme 2 (ACE2) as a SARS-CoV-2 receptor: molecular mechanisms and potential therapeutic target. Intensive Care Med. 2020 Apr;46(4):586-590. doi: 10.1007/s00134-020-05985-9. Epub 2020 Mar 3. PMID: 32125455; PMCID: PMC7079879.))
((Xu P, Sriramula S, Lazartigues E. ACE2/ANG-(1-7)/Mas pathway in the brain: the axis of good. Am J Physiol Regul Integr Comp Physiol. 2011 Apr;300(4):R804-17. doi: 10.1152/ajpregu.00222.2010. Epub 2010 Dec 22. PMID: 21178125; PMCID: PMC3075080.)).

The triad of neuroinvasion of SARS-CoV-2, induction of hypercoagulable state, and the inhibition of [[ACE2]] blocking the formation of [[Angiotensin]] serve as the pathophysiology for neurovascular insults.
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[[SARS-CoV-2]], which causes the [[Coronavirus Disease 2019]] ([[COVID-19]]) pandemic, has a brain [[neurotropism]] through binding to the [[Angiotensin-converting enzyme 2 receptor]] expressed by [[neuron]]es and [[glia]]l cells, including [[astrocyte]]s and [[microglia]]. Systemic infection which accompanies severe cases of COVID-19 also triggers substantial increase in circulating levels of [[chemokine]]s and [[interleukin]]s that compromise the [[blood-brain barrier]], enter the [[brain parenchyma]] and affect its defensive systems, [[astrocyte]]s and [[microglia]]. Brain areas devoid of a [[blood-brain barrier]] such as the circumventricular organs are particularly vulnerable to circulating inflammatory mediators. The performance of astrocytes and [[microglia]], as well as of immune cells required for brain health, is considered critical in defining the neurological damage and neurological outcome of COVID-19. In a review, they discussed the [[neurotropism]] of SARS-CoV-2, the implication of [[neuroinflammation]], adaptive and innate immunity, autoimmunity, as well as astrocytic and microglial immune and homeostatic functions in the neurological and psychiatric aspects of COVID-19. The consequences of SARS-CoV-2 infection during ageing, in the presence of systemic comorbidities, and for the exposed pregnant mother and foetus are also covered
((Tremblay ME, Madore C, Bordeleau M, Tian L, Verkhratsky A. Neuropathobiology of COVID-19: The Role for Glia. Front Cell Neurosci. 2020 Nov 11;14:592214. doi: 10.3389/fncel.2020.592214. PMID: 33304243; PMCID: PMC7693550.))