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However, their role on Aluminum chloride (AlCl\n                    <jats:sub>3<\/jats:sub>\n                    )-induced AD and amyloid \u03b2 (A\u03b2) clearance has not yet been fully elucidated. This research aimed to investigate the protective effectiveness of CV-loaded niosome (CV-LN) as a drug delivery system, in comparison to free form, against AlCl3-induced Alzheimer\u2019s-like neurodegeneration in rats with special emphasis on SIRT1\/miRNA-134\/GSK3\u03b2 axis. A niosomal formulation of Span 60, and cholesterol was chosen as an optimum formulation. Administration of CV or CV-LN dramatically improves the impaired oxidative markers, behavioral deficits, cholinergic and serotonergic dysfunctions, by significantly inhibiting monoamine oxidase, acetylcholinesterase activities and increasing serotonin level in brain of AlCl\n                    <jats:sub>3<\/jats:sub>\n                    -exposed rats. In parallel, CV or CV-LN triggers the activation of Sirtuin-1 (SIRT1) which downregulates miRNA-134, leading to increased brain-derived neurotrophic factor (BDNF) expression and improved neuronal survival and synaptic plasticity. Furthermore, CV or CV-LN decreases glycogen synthase kinase 3 beta (GSK3\u03b2)-mediated Tau hyperphosphorylation associated with clearance of A\u03b2. Additionally, CV or CV-LN significantly inhibits neuroinflammation by decreasing glial fibrillary acidic protein (GFAP), and apoptosis via modulating BAX, Caspase-3 and BCL2. Histopathological evaluations also supported the above findings. CV-LN formulations exhibited greater neuroprotective efficacy in a rat model, possibly due to better brain delivery and bioavailability. Eventually, CV and particularly CV-LN may hold promise as potential therapeutic candidates for further investigation in the context of neurodegenerative disorders and AD, possibly through modulation of SIRT1\/miRNA-134\/GSK3\u03b2 axis.\n                  <\/jats:p>","DOI":"10.1038\/s41598-025-25892-7","type":"journal-article","created":{"date-parts":[[2025,11,18]],"date-time":"2025-11-18T10:37:39Z","timestamp":1763462259000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Neuroprotective effects of Chlorella vulgaris loaded niosomes via SIRT1 activation in aluminum chloride-induced Alzheimer\u2019s model"],"prefix":"10.1038","volume":"15","author":[{"given":"Rania A.","family":"Radi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohamed A.","family":"Kandeil","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eman T.","family":"Mohammed","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marwa A.","family":"Ibrahim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amr","family":"Gamal","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abdel-Razik H.","family":"Abdel-Razik","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fatma","family":"Khalil","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dina","family":"Sabry","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,11,18]]},"reference":[{"key":"25892_CR1","doi-asserted-by":"publisher","first-page":"931","DOI":"10.1016\/j.biopha.2017.05.022","volume":"91","author":"Z Cao","year":"2017","unstructured":"Cao, Z., Wang, F., Xiu, C., Zhang, J. & Li, Y. 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