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Mitochondrial dysfunction, oxidative stress, and neuroinflammation are involved in the pathogenesis of depression. Notably, the renin\u2013angiotensin system (RAS) is involved in the pathogenesis of depression, and different findings revealed that angiotensin\u2010converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) may be effective in depression. However, the underlying mechanism for the role of dysregulated brain RAS\u2010induced depression remains speculative. Therefore, this review aimed to revise the conceivable role of ACEIs and ARBs and how these agents ameliorate the pathophysiology of depression. Dysregulation of brain RAS triggers the development and progression of depression through the reduction of brain 5HT and expression of brain\u2010derived neurotrophic factor (BDNF) and the induction of mitochondrial dysfunction, oxidative stress, and neuroinflammation. Therefore, inhibition of central classical RAS by ARBS and ACEIs and activation of non\u2010classical RAS prevent the development of depression by regulating 5HT, BDNF, mitochondrial dysfunction, oxidative stress, and neuroinflammation.<\/jats:p>","DOI":"10.1111\/cns.14525","type":"journal-article","created":{"date-parts":[[2023,11,13]],"date-time":"2023-11-13T00:38:55Z","timestamp":1699835935000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":48,"title":["Role of brain renin\u2013angiotensin system in depression: A new perspective"],"prefix":"10.1111","volume":"30","author":[{"given":"Naif H.","family":"Ali","sequence":"first","affiliation":[{"name":"Department of Internal Medicine Medical College Najran University  Najran KSA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hayder M.","family":"Al\u2010Kuraishy","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacology and Medicine, 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