{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T01:10:39Z","timestamp":1790730639561,"version":"4.1.0"},"reference-count":65,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2023,7,6]],"date-time":"2023-07-06T00:00:00Z","timestamp":1688601600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003750","name":"Association France Alzheimer","doi-asserted-by":"publisher","award":["R22002CC"],"award-info":[{"award-number":["R22002CC"]}],"id":[{"id":"10.13039\/501100003750","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001677","name":"Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001677","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Aging Cell"],"published-print":{"date-parts":[[2023,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Amyloid\u2010\u03b2 oligomers (A\u03b2o) are the most pathologically relevant A\u03b2 species in Alzheimer's disease (AD), because they induce early synaptic dysfunction that leads to learning and memory impairments. In contrast, increasing VEGF (Vascular Endothelial Growth Factor) brain levels have been shown to improve learning and memory processes, and to alleviate A\u03b2\u2010mediated synapse dysfunction. Here, we designed a new peptide, the blocking peptide (BP), which is derived from an A\u03b2o\u2010targeted domain of the VEGF protein, and investigated its effect on A\u03b2\u2010associated toxicity. Using a combination of biochemical, 3D and ultrastructural imaging, and electrophysiological approaches, we demonstrated that BP strongly interacts with A\u03b2o and blocks A\u03b2 fibrillar aggregation process, leading to the formation of A\u03b2 amorphous aggregates. BP further impedes the formation of structured A\u03b2o and prevents their pathogenic binding to synapses. Importantly, acute BP treatment successfully rescues long\u2010term potentiation (LTP) in the APP\/PS1 mouse model of AD, at an age when LTP is highly impaired in hippocampal slices. Moreover, BP is also able to block the interaction between A\u03b2o and VEGF, which suggests a dual mechanism aimed at both trapping A\u03b2o and releasing VEGF to alleviate A\u03b2o\u2010induced synaptic damage. Our findings provide evidence for a neutralizing effect of the BP on A\u03b2 aggregation process and pathogenic action, highlighting a potential new therapeutic strategy.<\/jats:p>","DOI":"10.1111\/acel.13907","type":"journal-article","created":{"date-parts":[[2023,7,7]],"date-time":"2023-07-07T04:40:13Z","timestamp":1688704813000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["A novel peptide derived from vascular endothelial growth factor prevents amyloid beta aggregation and toxicity"],"prefix":"10.1111","volume":"22","author":[{"given":"P.","family":"Bouvet","sequence":"first","affiliation":[{"name":"MeLiS, Institut NeuroMyoG\u00e8ne (INMG), Synaptopathies and Autoantibodies, Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale (INSERM), U1314 Centre National de la Recherche Scientifique (CNRS), UMR5284  Lyon France"},{"name":"Univ Lyon Universit\u00e9 Claude Bernard Lyon 1  Lyon France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P.","family":"de Gea","sequence":"additional","affiliation":[{"name":"MeLiS, Institut NeuroMyoG\u00e8ne (INMG), Synaptopathies and Autoantibodies, Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale (INSERM), U1314 Centre National de la Recherche Scientifique (CNRS), UMR5284  Lyon France"},{"name":"Univ Lyon Universit\u00e9 Claude Bernard Lyon 1  Lyon France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.","family":"Aimard","sequence":"additional","affiliation":[{"name":"MeLiS, Institut NeuroMyoG\u00e8ne (INMG), Synaptopathies and Autoantibodies, Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale (INSERM), U1314 Centre National de la Recherche Scientifique (CNRS), UMR5284  Lyon France"},{"name":"Univ Lyon Universit\u00e9 Claude Bernard Lyon 1  Lyon France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"N.","family":"Chounlamountri","sequence":"additional","affiliation":[{"name":"MeLiS, Institut NeuroMyoG\u00e8ne (INMG), Synaptopathies and Autoantibodies, Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale (INSERM), U1314 Centre National de la Recherche Scientifique (CNRS), UMR5284  Lyon France"},{"name":"Univ Lyon Universit\u00e9 Claude Bernard Lyon 1  Lyon France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J.","family":"Honnorat","sequence":"additional","affiliation":[{"name":"MeLiS, Institut NeuroMyoG\u00e8ne (INMG), Synaptopathies and Autoantibodies, Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale (INSERM), U1314 Centre National de la Recherche Scientifique (CNRS), UMR5284  Lyon France"},{"name":"Univ Lyon Universit\u00e9 Claude Bernard Lyon 1  Lyon France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J. G.","family":"Delcros","sequence":"additional","affiliation":[{"name":"Univ Lyon Universit\u00e9 Claude Bernard Lyon 1  Lyon France"},{"name":"Centre de Recherche en Canc\u00e9rologie de Lyon, Apoptosis, Cancer and Development, Institut PLAsCAN, INSERM U1052, CNRS UMR5286 Centre L\u00e9on B\u00e9rard  Lyon France"},{"name":"Centre de Recherche en Canc\u00e9rologie de Lyon, Small Molecules for Biological Targets INSERM U1052 \u2013 CNRS UMR5286, ISPB Rockefeller  Lyon France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P. 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