{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T10:12:42Z","timestamp":1791886362305,"version":"4.3.4"},"reference-count":52,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2025,4,28]],"date-time":"2025-04-28T00:00:00Z","timestamp":1745798400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["faseb.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The FASEB Journal"],"published-print":{"date-parts":[[2025,5,15]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Neuronal inflammation and apoptosis aggravate the secondary injury after spinal cord injury (SCI). Cathepsin L (CTSL) is a lysosomal cysteine protease with effects on the regulation of inflammation, but its role in SCI remains unclear. The in\u00a0vivo T10 mouse spinal cord contusion model was established. The results showed that CTSL expression was increased following SCI and then gradually decreased. Moreover, CTSL was mainly expressed in microglia. To detect the function of CTSL, after contusive injury, the mice were immediately injected with lentiviruses carrying CTSL shRNA. The results showed that CTSL depletion promoted functional recovery, accompanied by increased locomotor ability. CTSL deficiency reduced lesion cavity areas by inhibiting neuronal apoptosis and neuroinflammation. Indeed, CTSL deficiency decreased the secretion of TNF\u2010\u03b1, IL\u20106, and MCP\u20101 and M1 microglia polarization in the spinal cord. CTSL depletion inhibited the expression and assembly of NOD\u2010like receptor thermal protein domain associated protein 3 (NLRP3) inflammasome. In\u00a0vitro, CTSL expression was increased in LPS\u2010treated BV2 cells. CTSL silencing repressed LPS\u2010induced M1 polarization, as evidenced by the reduction in TNF\u2010\u03b1, IL\u20106, and MCP\u20101 expression in the supernatant of BV2 cells. CTSL knockdown induced the downregulation of NLRP3 expression and activation. The inhibition role of CTSL knockdown in microglial inflammation and M1 polarization was reversed by NLRP3 agonist. Collectively, the study suggests that CTSL induces the microglia M1 polarization\u2010mediated inflammation via promoting NLRP3 activation and thereby inhibits functional recovery after SCI.<\/jats:p>","DOI":"10.1096\/fj.202403101r","type":"journal-article","created":{"date-parts":[[2025,4,28]],"date-time":"2025-04-28T11:51:29Z","timestamp":1745841089000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Cathepsin L Aggravates Neuroinflammation via Promoting Microglia\n                    <scp>M1<\/scp>\n                    Polarization and\n                    <scp>NLRP3<\/scp>\n                    Activation After Spinal Cord Injury"],"prefix":"10.1096","volume":"39","author":[{"given":"Haocong","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Orthopaedics The General Hospital of Northern Theater Command  Shenyang Liaoning 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