{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T20:30:52Z","timestamp":1791664252800,"version":"4.3.4"},"reference-count":38,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2026,1,22]],"date-time":"2026-01-22T00:00:00Z","timestamp":1769040000000},"content-version":"vor","delay-in-days":21,"URL":"http:\/\/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\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82171378"],"award-info":[{"award-number":["82171378"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82401438"],"award-info":[{"award-number":["82401438"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100010877","name":"Science, Technology and Innovation Commission of Shenzhen Municipality","doi-asserted-by":"publisher","award":["JCYJ20240813114512016"],"award-info":[{"award-number":["JCYJ20240813114512016"]}],"id":[{"id":"10.13039\/501100010877","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100010877","name":"Science, Technology and Innovation Commission of Shenzhen Municipality","doi-asserted-by":"publisher","award":["JCYJ20240813152049062"],"award-info":[{"award-number":["JCYJ20240813152049062"]}],"id":[{"id":"10.13039\/501100010877","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["CNS Neurosci Ther"],"published-print":{"date-parts":[[2026,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Paclitaxel\u2010induced peripheral neuropathy (PIPN) is a severe and dose\u2010limiting side effect. This study investigated the therapeutic potential of Pituitary Adenylate Cyclase\u2010Activating Polypeptide (PACAP) and its underlying mechanism.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>A murine PIPN model was established. Behavioral tests assessed neuropathic pain. Molecular and cellular analyzes, including western blot, ELISA, and transmission electron microscopy, evaluated oxidative stress, mitochondrial function, and key protein expression in dorsal root ganglia (DRG) and SH\u2010SY5Y cells. The PGC\u20101\u03b1 inhibitor SR\u201018292 was used for mechanistic validation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>High\u2010dose PACAP (100\u2009\u03bcg\/kg) significantly alleviated PTX\u2010induced mechanical allodynia and thermal\/cold hyperalgesia. It reduced oxidative stress (lowered ROS\/MDA, increased SOD) and restored mitochondrial function (improved membrane potential, ATP, and ultrastructure) in DRG neurons. PACAP upregulated PGC\u20101\u03b1 and HO\u20101 expression, and its protective effects were abolished by PGC\u20101\u03b1 inhibition. Crucially, PACAP did not interfere with PTX's antitumor efficacy.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>PACAP alleviates PIPN by activating the PGC\u20101\u03b1 pathway to improve mitochondrial function and counteract oxidative stress, presenting a promising adjunct therapy that does not compromise chemotherapy.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/cns.70745","type":"journal-article","created":{"date-parts":[[2026,1,22]],"date-time":"2026-01-22T08:46:29Z","timestamp":1769071589000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["PACAP Alleviates Paclitaxel\u2010Induced Peripheral Neuropathy by Targeting Oxidative Stress and Mitochondrial Damage via the PGC\u20101\u03b1 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