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This study aims to explore the role of peroxisomes in Schwann cells in DN.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods<\/jats:title>\n            <jats:p>The abundance of peroxisomes in the sciatic nerves of mice or Schwann cells was analyzed using laser confocal super-resolution imaging and western blotting. The RFP-GFP-SKL (Ser-Lys-Leu) probe was utilized to assess pexophagy (peroxisomes autophagy) levels. To evaluate the palmitoylation of PEX11B, the acyl-resin assisted capture (acyl-RAC) assay and the Acyl-Biotin Exchange (ABE) assay were employed. Additionally, MR (Mendelian randomization) analysis was conducted to investigate the potential causal relationship between DN and MS (Multiple sclerosis).<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results<\/jats:title>\n            <jats:p>There was a decrease in peroxisomal abundance in the sciatic nerves of diabetic mice, and palmitic acid (PA) induced a reduction in peroxisomal abundance by inhibiting peroxisomal biogenesis in Schwann cells. Mechanistically, PA induced the palmitoylation of PEX11B at C25 site, disrupting its self-interaction and impeding peroxisome elongation. Fenofibrate, a PPAR\u03b1 agonist, effectively rescued peroxisomal dysfunction caused by PA and restored the peroxisomal abundance in diabetic mice. Lastly, MR analysis indicates a notable causal influence of DN on MS, with its onset and progression intricately linked to peroxisomal dysfunction.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p>Targeting the peroxisomal biogenesis pathway may be an effective strategy for preventing and treating DN, underscoring the importance of addressing MS risk at the onset of DN.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1186\/s12929-024-01115-5","type":"journal-article","created":{"date-parts":[[2025,2,12]],"date-time":"2025-02-12T00:02:21Z","timestamp":1739318541000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["PEX11B palmitoylation couples peroxisomal dysfunction with Schwann cells fail in diabetic neuropathy"],"prefix":"10.1186","volume":"32","author":[{"given":"Yu Mei","family":"Yang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hang Bin","family":"Ma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yue","family":"Xiong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qian","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6602-0974","authenticated-orcid":false,"given":"Xiu Kui","family":"Gao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,2,12]]},"reference":[{"key":"1115_CR1","doi-asserted-by":"publisher","first-page":"331","DOI":"10.1038\/ncpneuro0504","volume":"3","author":"G Said","year":"2007","unstructured":"Said G. 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