{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,30]],"date-time":"2026-10-30T07:30:30Z","timestamp":1793345430246,"version":"4.5.0"},"reference-count":41,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2026,6,12]],"date-time":"2026-06-12T00:00:00Z","timestamp":1781222400000},"content-version":"vor","delay-in-days":11,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T00:00:00Z","timestamp":1780272000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["CNS Neurosci Ther"],"published-print":{"date-parts":[[2026,6]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aim<\/jats:title>\n                    <jats:p>\n                      HIV transactivator of transcription (Tat) protein induces oxidative stress, neuroinflammation, and glial dysfunction in NeuroHIV. Ferroptosis, an iron\u2010dependent form of regulated cell death driven by lipid peroxidation, has emerged as a contributor to HIV\u2010associated neurocognitive disorders. This study aimed to determine whether hydrogen sulfide (H\n                      <jats:sub>2<\/jats:sub>\n                      S) mitigates HIV Tat\u2010induced ferroptosis in microglial cells.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      BV2 microglial cells were pretreated with sodium hydrosulfide (NaHS; 100\u2009\u03bcM), an H\n                      <jats:sub>2<\/jats:sub>\n                      S donor, followed by exposure to recombinant HIV Tat (100\u2009ng\/mL, 48\u2009h). Ferroptotic indices, including cytosolic Fe\n                      <jats:sup>2+<\/jats:sup>\n                      accumulation, lipid peroxidation, reactive oxygen species (ROS) generation, and cell membrane damage, were assessed using fluorescence\u2010based assays and lactate dehydrogenase (LDH) release. Expression of ferroptosis\u2010related and antioxidant proteins was analyzed by western blotting, and proinflammatory cytokine release was quantified by qPCR.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      NaHS pretreatment significantly attenuated HIV Tat\u2010induced Fe\n                      <jats:sup>2+<\/jats:sup>\n                      accumulation, ROS generation, lipid peroxidation, and LDH release. Mechanistically, NaHS suppressed pro\u2010ferroptotic mediators, acyl\u2010CoA synthetase long\u2010chain family member 4 (ACSL4) and 4\u2010hydroxynonenal (4\u2010HNE), while restoring solute carrier family 7\u2010member 11 (SLC7A11) and glutathione peroxidase 4 (GPX4) expression. NaHS also reduced HIV Tat\u2010induced IL1\u03b2, IL6, and TNF\u03b1 secretion.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      These findings demonstrate that H\n                      <jats:sub>2<\/jats:sub>\n                      S protects HIV Tat\u2010exposed microglia by suppressing ferroptosis and restoring cellular homeostasis. Collectively, these results identify H\n                      <jats:sub>2<\/jats:sub>\n                      S signaling as a promising mechanistic target for further investigation in NeuroHIV\u2010associated neuroinflammation.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/cns.70977","type":"journal-article","created":{"date-parts":[[2026,6,13]],"date-time":"2026-06-13T04:51:28Z","timestamp":1781326288000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Hydrogen Sulfide Rescues Microglia From\n                    <scp>HIV<\/scp>\n                    Tat\u2010Driven Ferroptosis: Implications for\n                    <scp>HIV<\/scp>\n                    \u2010Associated Neuroinflammation"],"prefix":"10.1002","volume":"32","author":[{"given":"Aitizaz Ul","family":"Ahsan","sequence":"first","affiliation":[{"name":"Department of Pharmacology and Experimental Neuroscience University of 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