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This review provides a comprehensive overview of the current understanding of distinct cell death modalities in animal models of depression and human brain tissues, with particular emphasis on their molecular mechanisms and pathological consequences. We further discuss the intricate interactions between cell death pathways and key pathological processes implicated in depression, including neuroinflammation, oxidative stress, mitochondrial dysfunction, and impaired neurotrophic support. In addition, we summarize emerging therapeutic strategies targeting cell death-associated signaling pathways, including pharmacological inhibition of specific cell death programs and modulation of shared upstream regulators. By integrating recent advances in molecular neuroscience and psychiatric research, this review provides a conceptual framework for elucidating the cellular mechanisms underlying depression and to highlight potential targets for the development of novel antidepressant therapies.<\/jats:p>","DOI":"10.3389\/fcell.2026.1966325","type":"journal-article","created":{"date-parts":[[2026,9,20]],"date-time":"2026-09-20T22:10:25Z","timestamp":1789942225000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Cell death pathways in the pathogenesis of depression: mechanisms and therapeutic implications"],"prefix":"10.3389","volume":"14","author":[{"given":"Yuting","family":"Xiong","sequence":"first","affiliation":[{"name":"Department of Nursing, Jiangxi University of Chinese Medicine","place":["Nanchang, Jiangxi, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuxin","family":"Zhang","sequence":"additional","affiliation":[{"name":"College of Integrated Traditional Chinese and Western Medicine, Jiangxi University of Chinese Medicine","place":["Nanchang, Jiangxi, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongxin","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Nursing, Jiangxi University of Chinese Medicine","place":["Nanchang, Jiangxi, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gui","family":"Xiao","sequence":"additional","affiliation":[{"name":"Department of Nursing, Jiangxi University of Chinese Medicine","place":["Nanchang, Jiangxi, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,9,21]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"114","DOI":"10.1016\/j.phrs.2017.04.028","article-title":"Antidepressants induce autophagy dependent-NLRP3-inflammasome inhibition in major depressive disorder","volume":"121","author":"Alcocer-G\u00f3mez","year":"2017","journal-title":"Pharmacol. 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