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The aim of the present study was to investigate the potential mechanisms by which TARDBP is involved in AD by promoting ferroptosis. An AD rat model was established by injecting homocysteine (Hcy). Memory function was assessed using the Morris water maze test and contextual fear conditioning test. Hippocampal neurons' morphology was observed by HE staining, and intracellular iron deposition in the hippocampus was evaluated by Perls' blue staining. PC12 cells were treated with 20\u2009\u03bcM A\u03b2\n                    <jats:sub>1\u201342<\/jats:sub>\n                    to establish an AD cell model in\u00a0vitro. Cell viability was measured by MTT assay; LDH release, intracellular ROS levels and Fe\n                    <jats:sup>2+<\/jats:sup>\n                    concentrations were determined. The mRNA stability of KRAS was assessed by actinomycin D assay. Activation of the MAP3K11\/SLC3A2\/GPX4 pathway was assessed by Western blot. Treatment with Fer\u20101 or down\u2010regulation of TARDBP improved memory function and reduced intracellular iron deposition in the hippocampus of AD rats. Furthermore, these interventions inhibited A\u03b2\n                    <jats:sub>1\u201342<\/jats:sub>\n                    \u2010induced PC12 cell damage, ROS production and iron accumulation. Mechanistically, down\u2010regulating TARDBP reduced the mRNA stability of KRAS, inhibited MAP3K11 expression and subsequently promoted the expression of SLC3A2 and GPX4. Conversely, up\u2010regulation of KRAS reversed the protective effects induced by TARDBP knockdown in both AD rats and A\u03b2\n                    <jats:sub>1\u201342<\/jats:sub>\n                    \u2010induced PC12 cells. TARDBP promotes the development of AD by enhancing the mRNA stability of KRAS, thereby mediating the MAP3K11\/SLC3A2\/GPX4 axis to induce ferroptosis.\n                  <\/jats:p>","DOI":"10.1111\/jcmm.71181","type":"journal-article","created":{"date-parts":[[2026,5,18]],"date-time":"2026-05-18T04:01:58Z","timestamp":1779076918000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["<scp>TARDBP<\/scp>\n                    Mediates the\n                    <scp>MAP<\/scp>\n                    3\n                    <scp>K<\/scp>\n                    11\/\n                    <scp>SLC<\/scp>\n                    3\n                    <scp>A<\/scp>\n                    2\/\n                    <scp>GPX<\/scp>\n                    4 Axis in Alzheimer's Disease Rats by Enhancing\n                    <scp>KRAS<\/scp>\n                    m\n                    <scp>RNA<\/scp>\n                    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