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CNEURO-201 (CN, also Amylovis-201) is a novel pharmaceutical agent with dual activity as an anti-amyloid-\u03b2 (A\u03b2) agent and \u03c31 receptor agonist. CN exhibits great efficacy at very low doses, delaying cognitive impairment and alleviating A\u03b2 load in animal models of AD. However, CN functions on other remains related to this pathology remain to be investigated. The present study sought to evaluate the effects of CN treatment at a dosage of 0.1 mg kg\u22121 (p.o) over an eight-week period in the 3xTg-AD mouse model. In silico studies, as well as biochemical and immunofluorescence assays, were conducted on brain tissue to investigate the CN effects on acetylcholine metabolism, redox system, and glial cell activation-related biomarkers in brain regions that are relevant for memory. The results demonstrated that CN effectively rescues cognitive impairment of 3xTg-AD mice by influencing glial activity to reduce existing A\u03b2 plaques but also modulating acetylcholine metabolism and the enzymatic response of proteins involved in the redox system. Our outcomes reinforced the potential of CN in treating AD by acting on multiple pathways altered in this disease.<\/jats:p>","DOI":"10.3390\/ijms26031301","type":"journal-article","created":{"date-parts":[[2025,2,3]],"date-time":"2025-02-03T12:18:56Z","timestamp":1738585136000},"page":"1301","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["CNEURO-201, an Anti-amyloidogenic Agent and \u03c31-Receptor Agonist, Improves Cognition in the 3xTg Mouse Model of Alzheimer\u2019s Disease by Multiple Actions in the Pathology"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7529-8476","authenticated-orcid":false,"given":"Humberto","family":"Mart\u00ednez-Orozco","sequence":"first","affiliation":[{"name":"Departamento de Neurobiolog\u00eda del Desarrollo y Neurofisiolog\u00eda, Instituto de Neurobiolog\u00eda-UNAM Campus Juriquilla, Boulevard Juriquilla 3001, Juriquilla 76230, Quer\u00e9taro, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alberto","family":"Bencomo-Mart\u00ednez","sequence":"additional","affiliation":[{"name":"Departamento de Farmacolog\u00eda, Centro de Neurociencias de Cuba, Avenida Independencia 8126, La Habana 11600, Cuba"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-3570-9255","authenticated-orcid":false,"given":"Juan Pablo","family":"Maya-Arteaga","sequence":"additional","affiliation":[{"name":"Departamento de Neurobiolog\u00eda del Desarrollo y Neurofisiolog\u00eda, Instituto de Neurobiolog\u00eda-UNAM Campus Juriquilla, Boulevard Juriquilla 3001, Juriquilla 76230, Quer\u00e9taro, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pedro Francisco","family":"Rubio-De Anda","sequence":"additional","affiliation":[{"name":"Departamento de Neurobiolog\u00eda del Desarrollo y Neurofisiolog\u00eda, Instituto de Neurobiolog\u00eda-UNAM Campus 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