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Our previous work found that TREM2 is highly expressed in microglia and is related to their functional state. However, the specific role of TREM2 in spinal cord injury has not yet been explored. To further investigate the potential mechanism of TREM2, we performed single\u2010cell sequencing on wild\u2010type (Wt) and\n                    <jats:italic>Trem2<\/jats:italic>\n                    <jats:sup>\n                      <jats:italic>\u2212\/\u2212<\/jats:italic>\n                    <\/jats:sup>\n                    mice before and after spinal cord injury. Compared to Wt mice, the lysosome, autophagy and membrane\u2010related pathways are more strongly activated in\n                    <jats:italic>Trem2<\/jats:italic>\n                    <jats:sup>\n                      <jats:italic>\u2212\/\u2212<\/jats:italic>\n                    <\/jats:sup>\n                    mice, suggesting that TREM2 may exert its effects by influencing lysosomal membranes and autophagy. Mechanistically, we demonstrated that the knockout of\n                    <jats:italic>Trem2<\/jats:italic>\n                    can reduce the nuclear translocation of TFEB by decreasing the phosphorylation of Syk. Furthermore, we validated that in\u00a0vitro and in\u00a0vivo silencing\n                    <jats:italic>Trem2<\/jats:italic>\n                    can promote autophagy by repairing lysosomal membrane permeabilization. Through immunofluorescence, 3D gait analysis, motor evoked potential experiments, H&amp;E staining and Masson staining, we demonstrated that the increased level of autophagy can rescue more microglia in\u00a0vivo and promote both functional and histological recovery of spinal cord injury. Collectively, these results not only suggest that microglial lysosomal autophagy is regulated in a TREM2\u2010dependent LMP manner, but also, more importantly, they provide a promising clinical translation strategy based on gene therapy for lysosome\u2010related central nervous system disorders.\n                  <\/jats:p>","DOI":"10.1111\/cpr.70047","type":"journal-article","created":{"date-parts":[[2025,5,5]],"date-time":"2025-05-05T02:18:10Z","timestamp":1746411490000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["<scp>TREM2<\/scp>\n                    Impedes Recovery After Spinal Cord Injury by Regulating Microglial Lysosomal Membrane Permeabilization\u2010Mediated Autophagy"],"prefix":"10.1111","volume":"58","author":[{"given":"Tianlun","family":"Zhao","sequence":"first","affiliation":[{"name":"Department of Spine Surgery The Third Affiliated Hospital of Sun Yat\u2010Sen University  Guangzhou China"},{"name":"Guangdong Provincial Center for Engineering and Technology Research of Minimally Invasive Spine Surgery  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiawei","family":"Di","sequence":"additional","affiliation":[{"name":"Department of Spine Surgery The Third Affiliated Hospital of Sun Yat\u2010Sen University  Guangzhou China"},{"name":"Guangdong Provincial Center for Engineering and Technology Research of Minimally Invasive Spine Surgery  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Kang","sequence":"additional","affiliation":[{"name":"Department of Spine Surgery The Third Affiliated Hospital of Sun Yat\u2010Sen University  Guangzhou China"},{"name":"Guangdong Provincial Center for Engineering and Technology Research of Minimally Invasive Spine Surgery  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haojie","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Spine Surgery The Third Affiliated Hospital of Sun Yat\u2010Sen University  Guangzhou China"},{"name":"Guangdong Provincial Center for Engineering and Technology Research of Minimally Invasive Spine Surgery  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Senyu","family":"Yao","sequence":"additional","affiliation":[{"name":"Department of Spine Surgery The Third Affiliated Hospital of Sun Yat\u2010Sen University  Guangzhou China"},{"name":"Guangdong Provincial Center for Engineering and Technology Research of Minimally Invasive Spine Surgery  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bin","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Spine Surgery The Third Affiliated Hospital of Sun Yat\u2010Sen University  Guangzhou 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