{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T13:10:38Z","timestamp":1791465038912,"version":"4.3.4"},"reference-count":151,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2025,1,8]],"date-time":"2025-01-08T00:00:00Z","timestamp":1736294400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"HUN-REN Hungarian Research Network"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Alzheimer\u2019s disease (AD) remains a leading cause of cognitive decline and mortality worldwide, characterized by neurodegeneration, synaptic deficiencies, and neuroinflammation. Despite advancements in early detection, diagnosis, and treatment, AD presents substantial challenges due to its complex pathology, heterogeneity, and the limited efficacy of current therapies. Consequently, there is a pressing need for novel therapeutic agents to target the multifaceted aspects of AD pathology, enhance current treatments, and minimize adverse effects. AdipoRon, an adiponectin receptor agonist, has garnered interest for its potential neuroprotective effects, including reducing neuroinflammation, improving mitochondrial function, and mitigating tau hyperphosphorylation. This review aimed to evaluate the effects of AdipoRon-based adiponectin replacement therapy against AD, using a comprehensive approach grounded in the PICO framework\u2014Population, Intervention, Comparison, and Outcomes. A total of six studies were reviewed, including in vitro and in vivo investigations examining AdipoRon\u2019s impact on various AD models. These studies involved different cell lines and transgenic mouse models, assessing various outcomes such as cognitive function, neuroinflammation, tau phosphorylation, synaptic deficiencies, and relevant molecular pathways. By synthesizing data from these studies, our review thoroughly explains AdipoRon\u2019s neuroprotective effects, mechanisms of action, and potential as a therapeutic agent for AD. This analysis aims to highlight the current state of knowledge, identify gaps in the research, and suggest directions for future studies and clinical applications.<\/jats:p>","DOI":"10.3390\/ijms26020484","type":"journal-article","created":{"date-parts":[[2025,1,8]],"date-time":"2025-01-08T11:56:22Z","timestamp":1736337382000},"page":"484","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["AdipoRon\u2019s Impact on Alzheimer\u2019s Disease\u2014A Systematic Review and Meta-Analysis"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5035-876X","authenticated-orcid":false,"given":"Sandra Maria","family":"Barbalho","sequence":"first","affiliation":[{"name":"Department of Biochemistry and Pharmacology, School of Medicine, Universidade de Mar\u00edlia (UNIMAR), Mar\u00edlia 17525-902, S\u00e3o Paulo, Brazil"},{"name":"Postgraduate Program in Structural and Functional Interactions in Rehabilitation, School of Medicine, Universidade de Mar\u00edlia (UNIMAR), Mar\u00edlia 17525-902, S\u00e3o Paulo, Brazil"},{"name":"Department of Biochemistry and Nutrition, School of Food and Technology of Mar\u00edlia (FATEC), Mar\u00edlia 17500-000, S\u00e3o Paulo, Brazil"},{"name":"UNIMAR Charity Hospital, Universidade de Mar\u00edlia (UNIMAR), Mar\u00edlia 17525-902, S\u00e3o Paulo, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3159-0982","authenticated-orcid":false,"given":"Lucas Fornari","family":"Laurindo","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Pharmacology, School of Medicine, Universidade de Mar\u00edlia (UNIMAR), Mar\u00edlia 17525-902, S\u00e3o Paulo, Brazil"},{"name":"Department of Biochemistry and Pharmacology, School of Medicine, Faculdade de Medicina de Mar\u00edlia (FAMEMA), Mar\u00edlia 17519-030, S\u00e3o Paulo, Brazil"},{"name":"Department of Administration, Associate Degree in Hospital Management, Universidade de Mar\u00edlia (UNIMAR), Mar\u00edlia 17525-902, S\u00e3o Paulo, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"B\u00e1rbara","family":"de Oliveira Zanuso","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Pharmacology, School of Medicine, Universidade de Mar\u00edlia (UNIMAR), Mar\u00edlia 17525-902, S\u00e3o Paulo, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rebeca Maria Siqueira","family":"da Silva","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Pharmacology, School of Medicine, Faculdade de Medicina de Mar\u00edlia (FAMEMA), Mar\u00edlia 17519-030, S\u00e3o Paulo, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L\u00edvia","family":"Gallerani Caglioni","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Pharmacology, School of Medicine, Faculdade de Medicina de Mar\u00edlia 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Brazil"},{"name":"Postgraduate Program in Structural and Functional Interactions in Rehabilitation, School of Medicine, Universidade de Mar\u00edlia (UNIMAR), Mar\u00edlia 17525-902, S\u00e3o Paulo, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caroline","family":"Barbalho Lamas","sequence":"additional","affiliation":[{"name":"Department of Gerontology, School of Gerontology, Universidade Federal de S\u00e3o Carlos (UFSCar), S\u00e3o Carlos 13565-905, S\u00e3o Paulo, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jesselina Francisco","family":"dos Santos Haber","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Pharmacology, School of Medicine, Universidade de Mar\u00edlia (UNIMAR), Mar\u00edlia 17525-902, S\u00e3o Paulo, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Virg\u00ednia Maria","family":"Cavallari Strozze Catharin","sequence":"additional","affiliation":[{"name":"Department 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