{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,24]],"date-time":"2026-07-24T08:06:04Z","timestamp":1784880364847,"version":"3.55.0"},"reference-count":79,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2026,7,24]],"date-time":"2026-07-24T00:00:00Z","timestamp":1784851200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Fondo Nacional de Financiamiento para la Ciencia, la Tecnolog\u00eda y la Innovaci\u00f3n Francisco Jos\u00e9 de Caldas, Minciencias","award":["112721-201-2024"],"award-info":[{"award-number":["112721-201-2024"]}]},{"name":"Comit\u00e9 para el Desarrollo de la Investigaci\u00f3n (CODI), Universidad de Antioquia","award":["2024-77129"],"award-info":[{"award-number":["2024-77129"]}]},{"name":"Programa J\u00f3venes Investigadores UdeA-2025"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Chronic stress is increasingly recognized as a major contributor to Alzheimer\u2019s disease (AD)-related neurodegeneration through mechanisms involving neuroinflammation, oxidative stress, mitochondrial dysfunction, excitotoxicity, and amyloidogenic processing. Here, we investigated the neuroprotective effects of Sesamum indicum whole paste extract (SIPE) using 2D neuron\u2013astrocyte-like cell (ALC) co-cultures and 3D neuron\u2013ALC spheroids exposed to a TNF-\u03b1\/glutamate\/cortisol (TGC) chronic stress paradigm. TGC exposure induced mitochondrial dysfunction, mitochondrial superoxide generation, astrocytic reactivity, NF-\u03baB activation, reduced pro-BDNF expression, intracellular and extracellular A\u03b242 accumulation, Tau phosphorylation, and caspase-3 activation, reproducing key hallmarks associated with chronic stress-related neurodegeneration. Among sesame-derived preparations evaluated, SIPE exhibited the strongest neuroprotective effects, preserving mitochondrial membrane potential, reducing oxidative stress, preventing neuronal loss, attenuating gliosis, and suppressing inflammatory, amyloidogenic, and apoptotic signaling. These effects were consistently reproduced in 3D spheroids. Phytochemical analysis revealed that SIPE contained the highest enrichment of sesamin, representing approximately 25% of the detected relative composition. Molecular docking analyses demonstrated favorable sesamin binding affinity toward TNF-\u03b1, DJ-1, A\u03b242, and caspase-3. Collectively, these findings identify SIPE as a promising multitarget neuroprotective strategy against chronic stress-associated AD-related pathology.<\/jats:p>","DOI":"10.3390\/biom16081084","type":"journal-article","created":{"date-parts":[[2026,7,24]],"date-time":"2026-07-24T07:36:13Z","timestamp":1784878573000},"page":"1084","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Neuroprotective Potential of Sesamum indicum in a Multifactorial In Vitro Neuron\u2013Astrocyte System Exposed to Chronic Stress Mediators"],"prefix":"10.3390","volume":"16","author":[{"given":"Viviana","family":"Soto-Mercado","sequence":"first","affiliation":[{"name":"Grupo de Neurociencias de Antioquia, Instituto de Investigaciones M\u00e9dicas, Facultad de Medicina, Sede de Investigaci\u00f3n Universitaria (SIU), Calle 62 No. 52-59, Torre 1, Laboratorios 411-412, Universidad de Antioquia (UdeA), Medellin 050010, Colombia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mar\u00eda Paulina","family":"Arias-Loaiza","sequence":"additional","affiliation":[{"name":"Grupo de Neurociencias de Antioquia, Instituto de Investigaciones M\u00e9dicas, Facultad de Medicina, Sede de Investigaci\u00f3n Universitaria (SIU), Calle 62 No. 52-59, Torre 1, Laboratorios 411-412, Universidad de Antioquia (UdeA), Medellin 050010, Colombia"},{"name":"Grupo de Investigaci\u00f3n la Pr\u00e1ctica de la Enfermer\u00eda en el Contexto Social-GIPECS, Departamento Formaci\u00f3n B\u00e1sica Profesional, Facultad de Enfermer\u00eda, Calle 67 #53-108, Universidad de Antioquia (UdeA), Medellin 050010, Colombia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8824-379X","authenticated-orcid":false,"given":"Miguel","family":"Mendivil-Perez","sequence":"additional","affiliation":[{"name":"Grupo de Neurociencias de Antioquia, Instituto de Investigaciones M\u00e9dicas, Facultad de Medicina, Sede de Investigaci\u00f3n Universitaria (SIU), Calle 62 No. 52-59, Torre 1, Laboratorios 411-412, Universidad de Antioquia (UdeA), Medellin 050010, Colombia"},{"name":"Grupo de Investigaci\u00f3n la Pr\u00e1ctica de la Enfermer\u00eda en el Contexto Social-GIPECS, Departamento Formaci\u00f3n B\u00e1sica Profesional, Facultad de Enfermer\u00eda, Calle 67 #53-108, Universidad de Antioquia (UdeA), Medellin 050010, Colombia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Nunez, S.G., Rabelo, S.P., Subotic, N., Caruso, J.W., and Knezevic, N.N. 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