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Osteopontin in Alzheimer's Disease: A Double-Edged Sword in Neurodegeneration and Neuroprotection—A Systematic Review Publisher Pubmed



Azizan Z1 ; Bazrgar M2 ; Bazgir N3 ; Moini SH1 ; Ghaseminejadkermani S4 ; Safa K4 ; Eshaghiandorcheh A5 ; Harirchian MH1
Authors
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Authors Affiliations
  1. 1. Department of Neurology, School of Medicine, Iranian Center of Neurological Research, Neuroscience Institute, Imam Khomeini Hospital, Tehran University of Medical Sciences, Tehran, Iran
  2. 2. Neuroscience Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran
  3. 3. Hearing Disorders Research Center, Loghman Hakim Hospital, Shahid Beheshti University of Medical Science, Tehran, Iran
  4. 4. Emergency Medicine Department, Shahid Beheshti University of Medical Science, Tehran, Iran
  5. 5. Kashani Hospital, Isfahan University of Medical Sciences, Isfahan, Iran

Source: CNS Neuroscience and Therapeutics Published:2025


Abstract

Background: Osteopontin (OPN) has emerged as a pivotal molecule in Alzheimer's disease (AD), with studies indicating its potential to act as both a neuroprotective agent and a contributor to neurodegeneration. This systematic review aims to elucidate the roles of OPN in AD pathogenesis through inflammatory pathways. Methods: We conducted a comprehensive analysis of current literature on OPN's involvement in AD, focusing on its signaling pathways, cellular interactions, and regulatory mechanisms. We searched PubMed, EMBASE, and Scopus databases by the keyword of Alzheimer's Disease and Osteopontin. Our date search was in 1990 until July 1, 2024 with no language limitation. Results: In a review of 758 studies, a total of 15 reports met the eligibility criteria and were included. Among the findings, four studies provided evidence supporting the protective mechanism of OPN within the context of AD. Eleven studies explain the inflammatory role of OPN. OPN has been shown to play a role in synaptic pruning, microglial activation, and the inflammatory processes associated with AD. Additionally, OPN is implicated in facilitating cellular communication and serves as a chemotactic molecule. It is suggested that the protective effects of OPN are predominantly mediated by the c fragment of the protein and are most prominent in the early stages of AD progression. Conclusion: OPN in AD has dual effects—protecting neurons and contributing to their degeneration. Future research should enhance its protective mechanisms, target specific signaling pathways, and develop therapies to slow AD progression. © 2025 The Author(s). CNS Neuroscience & Therapeutics published by John Wiley & Sons Ltd.