{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T03:21:27Z","timestamp":1790738487895,"version":"4.1.0"},"reference-count":56,"publisher":"MDPI AG","issue":"14","license":[{"start":{"date-parts":[[2022,7,12]],"date-time":"2022-07-12T00:00:00Z","timestamp":1657584000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Conselho Nacional de Ci\u00eancia e Tecnologia (CNPq)"},{"name":"Funda\u00e7\u00e3o de Amparo \u00e0 Pesquisa do Estado de Minas Gerais (FAPEMIG)"},{"name":"Coordena\u00e7\u00e3o de Aperfei\u00e7oamento de Pessoal de N\u00edvel Superior (CAPES)"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The Renin-Angiotensin System (RAS) is expressed in the central nervous system and has important functions that go beyond blood pressure regulation. Clinical and experimental studies have suggested that alterations in the brain RAS contribute to the development and progression of neurodegenerative diseases. However, there is limited information regarding the involvement of RAS components in Huntington\u2019s disease (HD). Herein, we used the HD murine model, (BACHD), as well as samples from patients with HD to investigate the role of both the classical and alternative axes of RAS in HD pathophysiology. BACHD mice displayed worse motor performance in different behavioral tests alongside a decrease in the levels and activity of the components of the RAS alternative axis ACE2, Ang-(1-7), and Mas receptors in the striatum, prefrontal cortex, and hippocampus. BACHD mice also displayed a significant increase in mRNA expression of the AT1 receptor, a component of the RAS classical arm, in these key brain regions. Moreover, patients with manifest HD presented higher plasma levels of Ang-(1-7). No significant changes were found in the levels of ACE, ACE2, and Ang II. Our findings provided the first evidence that an imbalance in the RAS classical and counter-regulatory arms may play a role in HD pathophysiology.<\/jats:p>","DOI":"10.3390\/ijms23147686","type":"journal-article","created":{"date-parts":[[2022,7,12]],"date-time":"2022-07-12T20:52:41Z","timestamp":1657659161000},"page":"7686","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Renin-Angiotensin System in Huntington\u2032s Disease: Evidence from Animal Models and Human Patients"],"prefix":"10.3390","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3678-118X","authenticated-orcid":false,"given":"Lucas M.","family":"Kangussu","sequence":"first","affiliation":[{"name":"Department of Morphology, Biological Science Institute, Federal University of Minas Gerais, Belo Horizonte 31270-901, MG, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natalia P.","family":"Rocha","sequence":"additional","affiliation":[{"name":"Department of Neurology, The Mitchell Center for Alzheimer\u2032s Disease and Related Brain Disorders, The University of Texas Health Science Center, Houston, TX 77030, USA"},{"name":"McGovern Medical School, HDSA Center of Excellence at The University of Texas Health Science Center, Houston, TX 77030, USA"},{"name":"Neuropsychiatry Program, Department of Psychiatry and Behavioral Sciences, McGovern Medical School, University of Texas, Houston, TX 77054, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Priscila A. C.","family":"Valad\u00e3o","sequence":"additional","affiliation":[{"name":"Department of Morphology, Biological Science Institute, Federal University of Minas Gerais, Belo Horizonte 31270-901, MG, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thatiane C. G.","family":"Machado","sequence":"additional","affiliation":[{"name":"Department of Morphology, Biological Science Institute, Federal University of Minas Gerais, Belo Horizonte 31270-901, MG, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3819-6355","authenticated-orcid":false,"given":"K\u00edvia B.","family":"Soares","sequence":"additional","affiliation":[{"name":"Department of Morphology, Biological Science Institute, Federal University of Minas Gerais, Belo Horizonte 31270-901, MG, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5788-6223","authenticated-orcid":false,"given":"Julliane V.","family":"Joviano-Santos","sequence":"additional","affiliation":[{"name":"Department of Morphology, Biological Science Institute, Federal University of Minas Gerais, Belo Horizonte 31270-901, MG, Brazil"},{"name":"Center for Mathematics, Computing, and Cognition (CMCC), Federal University of ABC (UFABC), S\u00e3o Bernardo do Campo 09612-000, SP, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leigh B.","family":"Latham","sequence":"additional","affiliation":[{"name":"McGovern Medical School, HDSA Center of Excellence at The University of Texas Health Science Center, Houston, TX 77030, USA"},{"name":"School of Medicine, University of Washington, Seattle, WA 98195, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabriela D.","family":"Colpo","sequence":"additional","affiliation":[{"name":"Neuropsychiatry Program, Department of Psychiatry and Behavioral Sciences, McGovern Medical School, University of Texas, Houston, TX 77054, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana Fl\u00e1via","family":"Almeida-Santos","sequence":"additional","affiliation":[{"name":"Department of Morphology, Biological Science Institute, Federal University of Minas Gerais, Belo Horizonte 31270-901, MG, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erin","family":"Furr Stimming","sequence":"additional","affiliation":[{"name":"McGovern Medical School, HDSA Center of Excellence at The University of Texas Health Science Center, Houston, TX 77030, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9222-3882","authenticated-orcid":false,"given":"Ana Cristina","family":"Sim\u00f5es e Silva","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, School of Medicine, Federal University of Minas Gerais, Belo Horizonte 30130-100, MG, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9621-5422","authenticated-orcid":false,"given":"Ant\u00f4nio L.","family":"Teixeira","sequence":"additional","affiliation":[{"name":"Neuropsychiatry Program, Department of Psychiatry and Behavioral Sciences, McGovern Medical School, University of Texas, Houston, TX 77054, USA"},{"name":"Department of Psychiatry & Behavioral Sciences, McGovern Medical School, University of Texas Health Science Center, Houston, TX 77054, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aline Silva","family":"Miranda","sequence":"additional","affiliation":[{"name":"Department of Morphology, Biological Science Institute, Federal University of Minas Gerais, Belo Horizonte 31270-901, MG, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristina","family":"Guatimosim","sequence":"additional","affiliation":[{"name":"Department of Morphology, Biological Science Institute, Federal University of Minas Gerais, Belo Horizonte 31270-901, MG, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,7,12]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"971","DOI":"10.1016\/0092-8674(93)90585-E","article-title":"A novel gene containing a trinucleotide repeat that is expanded and unstable on Huntington\u2019s disease chromosomes. 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