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So far, there is no efficient treatment for PTSD other than symptomatic palliative care. However, the cytoplasmic polyadenylation element binding protein\u20103 (CPEB3) has been recently associated with a potential risk gene for PTSD. Considering that the CPEB3 protein is a functional amyloid whose importance for long\u2010term memory consolidation in mammals is well established, we propose the active (amyloid) state of CPEB3 as a promising potential therapeutic target to investigate the blockade of the consolidation of traumatic memories using the anti\u2010amyloidogenic polyglutamine binding peptide 1 (QBP1). Here we report a genetic preclinical development evaluation in mice of this concept, providing a framework for future pharmacological treatment for PTSD based on the action of the QBP1 peptide. We first characterized the human CPEB3 (hCPEB3) protein in vitro, showing how its amyloid aggregation is inhibited by the active core of QBP1 (QBP1\u2010M8) without affecting other self\u2010assembly processes such as phase separation. Then, we generated and characterized a novel transgenic mouse that constitutively expresses QBP1 in tandem (TgQBP1). TgQBP1 mice exhibit impaired consolidation of simple learning after 24\u00a0h, affecting both hippocampus\u2010dependent and aversive memories. While recall of the fear context is reduced\u2014resulting in a lack of extinction\u2014QBP1 does not affect short\u2010term memory. Moreover, under a PTSD\u2010like protocol, TgQBP1 mice showed significant extinction of the traumatic memory and reduced anhedonia compared to WT mice, which showed the expected PTSD\u2010like symptoms of persistent aversive memory and anhedonia. Finally, the analysis of CPEB3 amyloid presence in extracted hippocampal samples showed a correlative decrease in murine CPEB3 oligomerization in the TgQBP1 mice. Taken together, these results strongly suggest that the amyloidogenic blockade of CPEB3 by the QBP1 peptide is a potential avenue for exploring future therapeutic approaches for the prevention and treatment of PTSD, pending validation through post\u2010developmental or pharmacological approaches.<\/jats:p>","DOI":"10.1002\/advs.202502541","type":"journal-article","created":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T09:03:42Z","timestamp":1792141422000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["An Anti\u2010Amyloidogenic Approach to Specifically Block Memory Consolidation in Mice for Therapeutic Intervention"],"prefix":"10.1002","author":[{"given":"Paula","family":"L\u00f3pez\u2010Garc\u00eda","sequence":"first","affiliation":[{"name":"Department of Molecular and Cellular Neurobiology Cajal Neuroscience Center (CNC\u2010CSIC) (formely Cajal Institute\u2010CSIC) Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kerry R.","family":"McGreevy","sequence":"additional","affiliation":[{"name":"Department of Translational Neuroscience Cajal Neuroscience Center (CNC\u2010CSIC) (formely Cajal Institute\u2010CSIC) Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Eugenia","family":"Vaquero","sequence":"additional","affiliation":[{"name":"Department of Molecular and Cellular Neurobiology Cajal Neuroscience Center (CNC\u2010CSIC) (formely Cajal Institute\u2010CSIC) Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan M.","family":"Suarez\u2010Rivero","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology and Biochemical Engineering Universidad Pablo de Olavide  Seville Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonio","family":"Moreno\u2010Rodr\u00edguez","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology and Biochemical Engineering Universidad Pablo de Olavide  Seville Spain"},{"name":"Andalusian Centre for Developmental Biology (CABD, UPO\u2010CSIC\u2010JA)  Seville Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonio J.","family":"P\u00e9rez\u2010Pulido","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology and Biochemical Engineering Universidad Pablo de Olavide  Seville Spain"},{"name":"Andalusian Centre for Developmental Biology (CABD, UPO\u2010CSIC\u2010JA)  Seville Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel Ram\u00edrez","family":"de Mingo","sequence":"additional","affiliation":[{"name":"Department of Molecular and Cellular Neurobiology Cajal Neuroscience Center (CNC\u2010CSIC) (formely Cajal Institute\u2010CSIC) Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Pall\u00e9","sequence":"additional","affiliation":[{"name":"Department of Translational Neuroscience Cajal Neuroscience Center (CNC\u2010CSIC) (formely Cajal Institute\u2010CSIC) Madrid Spain"},{"name":"Salk Institute for Biological Studies  La Jolla California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helena Akiko","family":"Popiel","sequence":"additional","affiliation":[{"name":"National Center of Neurology and Psychiatry. National Institute of Neuroscience Department of Degenerative Neurological Diseases Kodaira, Tokyo Japan"},{"name":"Center for International Education and Research Tokyo Medical University  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Santi","sequence":"additional","affiliation":[{"name":"Department of Psychological &amp; Brain Sciences Johns Hopkins University  Baltimore Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mario D.","family":"Cordero","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology and Biochemical Engineering Universidad Pablo de Olavide  Seville Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jos\u00e9 Luis","family":"Trejo","sequence":"additional","affiliation":[{"name":"Department of Translational Neuroscience Cajal Neuroscience Center (CNC\u2010CSIC) (formely Cajal Institute\u2010CSIC) Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshitaka","family":"Nagai","sequence":"additional","affiliation":[{"name":"National Center of Neurology and Psychiatry. National Institute of Neuroscience Department of Degenerative Neurological Diseases Kodaira, Tokyo Japan"},{"name":"Graduate School of Medicine Department of Neurotherapeutics Osaka University  Suita Osaka Japan"},{"name":"Faculty of Medicine Department of Neurology\u00a0and Life Science Research Institute Kindai University  Sakai Osaka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7319-406X","authenticated-orcid":false,"given":"Mariano","family":"Carri\u00f3n\u2010V\u00e1zquez","sequence":"additional","affiliation":[{"name":"Department of Molecular and Cellular Neurobiology Cajal Neuroscience Center (CNC\u2010CSIC) (formely Cajal Institute\u2010CSIC) Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,10,16]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"crossref","DOI":"10.1176\/appi.books.9780890425596","volume-title":"Diagnostic and Statistical Manual of Mental Disorders","author":"A. 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