{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,29]],"date-time":"2026-06-29T05:48:07Z","timestamp":1782712087971,"version":"3.54.5"},"reference-count":86,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,6,29]],"date-time":"2026-06-29T00:00:00Z","timestamp":1782691200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Aging Neurosci."],"abstract":"<jats:p>\n                    The buildup of toxic aggregates formed by the amyloid-\u03b2 peptide 1\u201342 (A\u03b2\n                    <jats:sub>42<\/jats:sub>\n                    ) is a central process in Alzheimer\u2019s disease (AD) pathology. The peptide\u2019s self-assembly and toxicity are highly dependent on its primary amino acid sequence and can be altered by modifying key residues. Specifically, the single amino acid substitutions A30W, K28A, and M35C can reduce the aggregation and toxicity of the A\u03b2\n                    <jats:sub>42<\/jats:sub>\n                    peptide. In this study, we further evaluated the effects of these mutations in a C6 rat glioma cell line and in the\n                    <jats:italic>Caenorhabditis elegans<\/jats:italic>\n                    strains CL2006 and CL4176, which express muscular A\u03b2\n                    <jats:sub>42<\/jats:sub>\n                    as an\n                    <jats:italic>in vivo<\/jats:italic>\n                    model. Our results showed that the A30W, K28A, and M35C substitutions reduce apoptosis induction in cell culture, in contrast to the WT A\u03b242 peptide. In\n                    <jats:italic>C. elegans<\/jats:italic>\n                    , the three variants extended the lifespan of CL2006 worms by reducing fibrillar aggregates or altering aging, whereas the M35C peptide delayed the paralysis of CL4176 worms. Additionally, the substitutions altered oxidative stress and autophagy in control worms. Taken together, these results suggest that the A30W, K28A, and M35C substitutions reduce A\u03b242 toxicity in cell culture and in\n                    <jats:italic>C. elegans<\/jats:italic>\n                    and could protect the nematode against A\u03b242 toxicity.\n                  <\/jats:p>","DOI":"10.3389\/fnagi.2026.1843210","type":"journal-article","created":{"date-parts":[[2026,6,29]],"date-time":"2026-06-29T05:40:53Z","timestamp":1782711653000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["The amino acid substitutions A30W, K28A, and M35C alter amyloid-\u03b2 peptide toxicity in cell culture and in an in vivo model of amyloidosis in Caenorhabditis elegans"],"prefix":"10.3389","volume":"18","author":[{"given":"Diana Patricia","family":"Quijano-Guerrero","sequence":"first","affiliation":[{"name":"Laboratorio de Inmunolog\u00eda y Virolog\u00eda, Departamento de Microbiolog\u00eda e Inmunolog\u00eda, Facultad de Ciencias Biol\u00f3gicas, Universidad Aut\u00f3noma de Nuevo Le\u00f3n, San Nicol\u00e1s de los Garza","place":["Nuevo Le\u00f3n, Mexico"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana Esther","family":"Estrada-Rodr\u00edguez","sequence":"additional","affiliation":[{"name":"School of Medicine, University of Monterrey (UDEM), San Pedro Garza Garc\u00eda","place":["Nuevo Le\u00f3n, Mexico"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mauricio","family":"Caballero-Rodr\u00edguez","sequence":"additional","affiliation":[{"name":"School of Medicine, University of Monterrey (UDEM), San Pedro Garza Garc\u00eda","place":["Nuevo Le\u00f3n, Mexico"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Danna Loretta","family":"de Le\u00f3n-Rivera","sequence":"additional","affiliation":[{"name":"School of Medicine, University of Monterrey (UDEM), San Pedro Garza Garc\u00eda","place":["Nuevo Le\u00f3n, Mexico"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristina","family":"Rodr\u00edguez-Padilla","sequence":"additional","affiliation":[{"name":"Laboratorio de Inmunolog\u00eda y Virolog\u00eda, Departamento de Microbiolog\u00eda e Inmunolog\u00eda, Facultad de Ciencias Biol\u00f3gicas, Universidad Aut\u00f3noma de Nuevo Le\u00f3n, San Nicol\u00e1s de los Garza","place":["Nuevo Le\u00f3n, Mexico"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Victor Julian","family":"Valdes","sequence":"additional","affiliation":[{"name":"Department of Cell Biology and Development, Institute of Cellular Physiology (IFC), National Autonomous University of Mexico (UNAM)","place":["Mexico City, Mexico"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diana","family":"Caballero-Hern\u00e1ndez","sequence":"additional","affiliation":[{"name":"Laboratorio de Inmunolog\u00eda y Virolog\u00eda, Departamento de Microbiolog\u00eda e Inmunolog\u00eda, Facultad de Ciencias Biol\u00f3gicas, Universidad Aut\u00f3noma de Nuevo Le\u00f3n, San Nicol\u00e1s de los Garza","place":["Nuevo Le\u00f3n, Mexico"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rom\u00e1n","family":"Vidaltamayo","sequence":"additional","affiliation":[{"name":"School of Medicine, University of Monterrey (UDEM), San Pedro Garza Garc\u00eda","place":["Nuevo Le\u00f3n, Mexico"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana Carolina","family":"Mart\u00ednez-Torres","sequence":"additional","affiliation":[{"name":"Laboratorio de Inmunolog\u00eda y Virolog\u00eda, Departamento de Microbiolog\u00eda e Inmunolog\u00eda, Facultad de Ciencias Biol\u00f3gicas, Universidad Aut\u00f3noma de Nuevo Le\u00f3n, San Nicol\u00e1s de los Garza","place":["Nuevo Le\u00f3n, Mexico"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Viviana","family":"Zomosa-Signoret","sequence":"additional","affiliation":[{"name":"School of Medicine, University of Monterrey (UDEM), San Pedro Garza Garc\u00eda","place":["Nuevo Le\u00f3n, Mexico"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,6,29]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"465","DOI":"10.1016\/j.ymeth.2014.04.002","article-title":"The C. elegans lifespan assay toolkit.","volume":"68","author":"Amrit","year":"2014","journal-title":"Methods"},{"key":"B2","doi-asserted-by":"publisher","first-page":"282","DOI":"10.1016\/j.expneurol.2005.08.001","article-title":"Amyloid-beta causes apoptosis of neuronal cells via caspase cascade, which can be prevented by amyloid-beta-derived short peptides.","volume":"196","author":"Awasthi","year":"2005","journal-title":"Exp. 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