{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T09:06:31Z","timestamp":1789635991624,"version":"4.0.0"},"reference-count":52,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T00:00:00Z","timestamp":1789603200000},"content-version":"vor","delay-in-days":259,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,1,1]],"date-time":"2026-01-01T00:00:00Z","timestamp":1767225600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100004704","name":"National Research Council of Thailand","doi-asserted-by":"publisher","award":["N42A670287"],"award-info":[{"award-number":["N42A670287"]}],"id":[{"id":"10.13039\/501100004704","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002873","name":"Chulalongkorn University","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100002873","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Oxidative Medicine and Cellular Longevity"],"published-print":{"date-parts":[[2026,1]]},"abstract":"<jats:p>\n                    Oxidative stress is a central pathological mechanism in neurodegenerative diseases (NDDs), contributing to mitochondrial dysfunction, impaired proteostasis, and progressive neuronal loss. The sigma\u20101 receptor (S1R) is an endoplasmic reticulum (ER)\u2010resident chaperone that coordinates cellular stress responses and has emerged as a promising therapeutic target for neuroprotection. In this study, we investigated the neuroprotective properties and mechanisms of the structurally related N\u2010benzylamides, N\u2010benzylcinnamide (NBCA) and N\u2010benzylbenzamide (NBBA) using complementary in vitro, in vivo and in silico approaches. Neuroprotective activity was initially evaluated using glutamate\u2010induced oxidative injury in HT22 hippocampal neurones and H\n                    <jats:sub>2<\/jats:sub>\n                    O\n                    <jats:sub>2<\/jats:sub>\n                    \u2010induced oxidative stress in SH\u2010SY5Y neuroblastoma cells. Both compounds significantly attenuated oxidative injury, although NBCA consistently showed greater efficacy and was therefore selected for detailed mechanistic investigation. NBCA reduced intracellular reactive oxygen species (ROS) production and lipid peroxidation while restoring endogenous antioxidant enzyme activities, mitochondrial membrane potential, ATP production, and cholinergic homeostasis. Immunofluorescence analysis showed that NBCA modulated nuclear factor erythroid 2\u2010related factor 2 (NRF2) and S1R immunoreactivity after oxidative stress. NBCA also promoted neurite outgrowth in wild\u2010type (WT) Neuro\u20102a cells, whereas these effects were absent in S1R knockout cells, supporting the involvement of S1R\u2010associated signalling. Molecular docking predicted favourable interactions between NBCA and the stress\u2010response proteins S1R, BiP and TMEM97, suggesting modulation of interconnected cellular stress\u2010response networks. In\n                    <jats:italic>Caenorhabditis elegans<\/jats:italic>\n                    , NBCA improved resistance to oxidative stress, preserved learning and memory, delayed amyloid\u2010\u03b2\u2010induced paralysis, and reduced amyloid deposition in transgenic Alzheimer\u2019s disease (AD) models. Collectively, these findings demonstrate that NBCA exerts neuroprotective effects across multiple experimental models by preserving redox homeostasis, mitochondrial function, and neuronal integrity. The convergence of pharmacological, genetic, imaging, computational, and whole\u2010organism evidence supports the involvement of S1R\u2010associated signalling in NBCA\u2019s biological activity. Together, these findings demonstrate that modulation of S1R\u2010associated cellular stress\u2010response networks is a promising strategy for preserving neuronal function during oxidative stress and neurodegeneration and identify NBCA as a valuable lead compound for future mechanistic and therapeutic investigation.\n                  <\/jats:p>","DOI":"10.1155\/omcl\/3092494","type":"journal-article","created":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T08:53:16Z","timestamp":1789635196000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Neuroprotective Effects of Two N\u2010Benzylamides in Models of Oxidative Stress, Neurite Outgrowth and Neurodegeneration"],"prefix":"10.1155","volume":"2026","author":[{"given":"Subaraja","family":"Mamangam","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anantha Krishnan","family":"Dhanabalan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kanika","family":"Verma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0956-0410","authenticated-orcid":false,"given":"Mani Iyer","family":"Prasanth","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sirikalaya","family":"Brimson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2074-8262","authenticated-orcid":false,"given":"James Michael","family":"Brimson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,9,17]]},"reference":[{"key":"e_1_2_11_1_2","doi-asserted-by":"publisher","DOI":"10.3390\/ijms21165646"},{"key":"e_1_2_11_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neubiorev.2022.104961"},{"key":"e_1_2_11_3_2","doi-asserted-by":"publisher","DOI":"10.3390\/antiox11081511"},{"key":"e_1_2_11_4_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12964-024-01791-8"},{"key":"e_1_2_11_5_2","doi-asserted-by":"crossref","unstructured":"LiuJ.andYangB. 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