{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,29]],"date-time":"2026-08-29T15:25:43Z","timestamp":1788017143907,"version":"build-2784847793"},"reference-count":123,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2023,8,4]],"date-time":"2023-08-04T00:00:00Z","timestamp":1691107200000},"content-version":"vor","delay-in-days":215,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100008973","name":"University of Kurdistan","doi-asserted-by":"publisher","award":["1400"],"award-info":[{"award-number":["1400"]}],"id":[{"id":"10.13039\/501100008973","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Analytical Cellular Pathology"],"published-print":{"date-parts":[[2023,1]]},"abstract":"<jats:p>Angiotensin\u2010converting enzyme 2 (ACE2), a key enzyme in the renin\u2013angiotensin 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\u2010CoV\u20102), the virus responsible for coronavirus disease\u20102019 (COVID\u201019), binds to ACE2, which raises concerns about the potential for viral infection in the CNS. There are numerous reports suggesting a link between SARS\u2010CoV\u20102 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\u2010CoV\u20102 infection. Several routes of SARS\u2010CoV\u20102 entry into the brain have been proposed. Because an anosmia condition appeared broadly in COVID\u201019 patients, the olfactory nerve route was suggested as an early pathway for SARS\u2010CoV\u20102 entry into the brain. In addition, a hematogenous route via disintegrations in the blood\u2013brain 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\u201019 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\u2010CoV\u20102 infection, at least in part. Downregulation of ACE2 due to SARS\u2010CoV\u20102 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\u2010releasing hormone. SARS\u2010CoV\u20102 infection may also dysregulate the CNS neurotransmission, leading to neurological complications observed in severe cases of COVID\u201019. It can be concluded that the neurological manifestations of COVID\u201019 may be partially associated with changes in brain RAS components.<\/jats:p>","DOI":"10.1155\/2023\/8883492","type":"journal-article","created":{"date-parts":[[2023,8,4]],"date-time":"2023-08-04T20:50:09Z","timestamp":1691182209000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Brain Renin\u2013Angiotensin System: From Physiology to Pathology in Neuronal Complications Induced by 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