{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T20:47:08Z","timestamp":1790714828779,"version":"4.1.0"},"reference-count":62,"publisher":"MDPI AG","issue":"21","license":[{"start":{"date-parts":[[2021,10,26]],"date-time":"2021-10-26T00:00:00Z","timestamp":1635206400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"H2020 SME Phase 1","award":["-"],"award-info":[{"award-number":["-"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>We present here a gene therapy approach aimed at preventing the formation of Ca2+-permeable amyloid pore oligomers that are considered as the most neurotoxic structures in both Alzheimer\u2019s and Parkinson\u2019s diseases. Our study is based on the design of a small peptide inhibitor (AmyP53) that combines the ganglioside recognition properties of the \u03b2-amyloid peptide (A\u03b2, Alzheimer) and \u03b1-synuclein (\u03b1-syn, Parkinson). As gangliosides mediate the initial binding step of these amyloid proteins to lipid rafts of the brain cell membranes, AmyP53 blocks, at the earliest step, the Ca2+ cascade that leads to neurodegeneration. Using a lentivirus vector, we genetically modified brain cells to express the therapeutic coding sequence of AmyP53 in a secreted form, rendering these cells totally resistant to oligomer formation by either A\u03b2 or \u03b1-syn. This protection was specific, as control mCherry-transfected cells remained fully sensitive to these oligomers. AmyP53 was secreted at therapeutic concentrations in the supernatant of cultured cells, so that the therapy was effective for both transfected cells and their neighbors. This study is the first to demonstrate that a unique gene therapy approach aimed at preventing the formation of neurotoxic oligomers by targeting brain gangliosides may be considered for the treatment of two major neurodegenerative disorders, Alzheimer\u2019s and Parkinson\u2019s diseases.<\/jats:p>","DOI":"10.3390\/ijms222111550","type":"journal-article","created":{"date-parts":[[2021,10,26]],"date-time":"2021-10-26T23:54:33Z","timestamp":1635292473000},"page":"11550","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Gene Therapy Strategy for Alzheimer\u2019s and Parkinson\u2019s Diseases Aimed at Preventing the Formation of Neurotoxic Oligomers in SH-SY5Y Cells"],"prefix":"10.3390","volume":"22","author":[{"given":"Assou","family":"El-Battari","sequence":"first","affiliation":[{"name":"INSERM UMR_S 1072, Aix-Marseille Universit\u00e9, 13015 Marseille, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L\u00e9a","family":"Rodriguez","sequence":"additional","affiliation":[{"name":"CUO-Recherche, D\u00e9partement d\u2019ophtalmologie, Facult\u00e9 de M\u00e9decine, Universit\u00e9 Laval and Centre de recherche du CHU de Qu\u00e9bec-Universit\u00e9 Laval, Qu\u00e9bec, QC G1V 0A6, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9516-4168","authenticated-orcid":false,"given":"Henri","family":"Chahinian","sequence":"additional","affiliation":[{"name":"INSERM UMR_S 1072, Aix-Marseille Universit\u00e9, 13015 Marseille, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8308-6975","authenticated-orcid":false,"given":"Olivier","family":"Del\u00e9zay","sequence":"additional","affiliation":[{"name":"Facult\u00e9 de M\u00e9decine, SAINBIOSE INSERM U1059, Campus Sant\u00e9 Innovations, 42270 St. Priest en Jarez, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacques","family":"Fantini","sequence":"additional","affiliation":[{"name":"INSERM UMR_S 1072, Aix-Marseille Universit\u00e9, 13015 Marseille, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nouara","family":"Yahi","sequence":"additional","affiliation":[{"name":"INSERM UMR_S 1072, Aix-Marseille Universit\u00e9, 13015 Marseille, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0655-7056","authenticated-orcid":false,"given":"Coralie","family":"Di Scala","sequence":"additional","affiliation":[{"name":"Neuroscience Center\u2014HiLIFE, Helsinki Institute of Life Science, University of Helsinki, 00014 Helsinki, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,10,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"S3","DOI":"10.3233\/JPD-181474","article-title":"The Emerging Evidence of the Parkinson Pandemic","volume":"8","author":"Dorsey","year":"2018","journal-title":"J. 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