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It is made up of two axes: one is the Angiotensin II Type 1 receptor (AT1R) or Angiotensin II Type 2 receptor (AT2R), while the other is angiotensin-(1-7) [Ang-(1-7)], and Mas receptor; the latter has reported developing a neuroprotective effect; oppositely, AT1R activation has been linked to neurodegenerative diseases. This study aims to elucidate the potential neuroprotective effect of Candesartan (Cand) an AT1R blocker in mitigating neuronal degeneration caused by 3-Nitropropionic acid (3NP) induced HD by revealing the prospective role of Ang II\/AT2R\/Ang-(1-7)\/Mas receptor, CREB\/BDNF\/PGC1-\u03b1 besides JNK\/c-Jun trajectories, as well as the anti-apoptotic survivin. HD was induced by 3NP (10 mg\/kg) for 14 days. Rats received Candesartan (2.5 or 5 mg\/kg) for 14 days, after which brain and striatum were isolated for the histopathological, immunohistochemical, and biochemical analysis. Cand displayed significant improvement in the rats\u2019 behavioral tests, enhancing their memory, motor, and cognitive functions induced by 3NP, which was confirmed by the striatal histopathological and immunohistochemical examination of the GFAP. In addition, Cand activated the Ang II\/AT2R\/Ang-(1-7)\/Mas receptor axis. Moreover, Cand stimulated the production of striatal neurotrophic proteins CREB\/BDNF\/PGC1-\u03b1 which in turn decreased the levels of inflammatory mediators NF-\u03baB and IL-1\u03b2, accompanied by an increase in the antioxidants NQO1 and HO-1 levels. Similarly, Cand led to the inhibition of the JNK\/c-Jun with activation of survivin. In conclusion, Candesartan has mitigated the striatal degeneration and mitochondrial dysfunction induced by 3NP through various mechanistic pathways.<\/jats:p>","DOI":"10.1007\/s10787-025-01889-6","type":"journal-article","created":{"date-parts":[[2025,9,16]],"date-time":"2025-09-16T08:41:20Z","timestamp":1758012080000},"page":"6231-6249","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Neuroprotective effects of candesartan in 3-nitropropionic acid-induced Huntington\u2019s disease: modulation of angiotensin and CREB\/BDNF\/PGC1-\u03b1 signaling"],"prefix":"10.1007","volume":"33","author":[{"given":"Ali M.","family":"Elgindy","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ahmed M.","family":"Atwa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"El-Sayed E.","family":"El-Awady","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0432-3152","authenticated-orcid":false,"given":"Norhan M.","family":"El-Sayed","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naglaa F.","family":"El-Orabi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,9,16]]},"reference":[{"issue":"13","key":"1889_CR1","doi-asserted-by":"crossref","first-page":"2657","DOI":"10.1093\/nar\/25.13.2657","volume":"25","author":"I Afonina","year":"1997","unstructured":"Afonina I et al (1997) Efficient priming of PCR with short oligonucleotides conjugated to a minor groove binder. 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