{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T05:41:23Z","timestamp":1788327683147,"version":"build-2803163510"},"reference-count":87,"publisher":"American Society for Clinical Investigation","issue":"12","license":[{"start":{"date-parts":[[2025,6,23]],"date-time":"2025-06-23T00:00:00Z","timestamp":1750636800000},"content-version":"vor","delay-in-days":46,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001677","name":"INSERM","doi-asserted-by":"crossref","award":["ATIP-AVENIR"],"award-info":[{"award-number":["ATIP-AVENIR"]}],"id":[{"id":"10.13039\/501100001677","id-type":"DOI","asserted-by":"crossref"}]},{"name":"REGION REUNION","award":["PhD grant"],"award-info":[{"award-number":["PhD grant"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,6,23]]},"abstract":"<jats:p>\n                    Proprotein convertase subtilisin\/kexin type 9 (\n                    <jats:italic>PCSK9<\/jats:italic>\n                    ) induces the hepatic degradation of the low-density lipoprotein receptor (\n                    <jats:italic>LDLR<\/jats:italic>\n                    ), thereby increasing the concentration of LDL-cholesterol in the blood. Beyond its effects on LDL, recent studies have reported pleiotropic effects of\n                    <jats:italic>PCSK9<\/jats:italic>\n                    , notably in septic shock, vascular inflammation, viral infection, and cancer. While the functional and structural integrity of peripheral nerves are critically influenced by circulating lipids, the effect of\n                    <jats:italic>PCSK9<\/jats:italic>\n                    on the peripheral nervous system remains unknown. In this study, we investigated the consequences of\n                    <jats:italic>PCSK9<\/jats:italic>\n                    deficiency on peripheral nerves. We found that\n                    <jats:italic>PCSK9<\/jats:italic>\n                    deletion in mice leads to peripheral neuropathy, characterized by reduced thermal and mechanical pain sensations.\n                    <jats:italic>PCSK9<\/jats:italic>\n                    -deficient mice also presented with skin structural changes, including a reduction in nociceptive Schwann cell number, axonal swelling of Remak fibers, and hypomyelination of small nerve fibers. Interestingly, the peripheral nerves of\n                    <jats:italic>PCSK9<\/jats:italic>\n                    -deficient mice showed an upregulation of\n                    <jats:italic>CD36<\/jats:italic>\n                    , a fatty acid transporter, which correlated with increased nerve lipid content, structural mitochondrial abnormalities, and acylcarnitine accumulation. Our findings demonstrate that\n                    <jats:italic>PCSK9<\/jats:italic>\n                    plays a critical role in peripheral nerves by regulating lipid homeostasis and that its deficiency results in symptoms related to peripheral neuropathy.\n                  <\/jats:p>","DOI":"10.1172\/jci.insight.183786","type":"journal-article","created":{"date-parts":[[2025,5,8]],"date-time":"2025-05-08T12:00:21Z","timestamp":1746705621000},"source":"Crossref","is-referenced-by-count":7,"title":["PCSK9 deficiency promotes the development of peripheral neuropathy"],"prefix":"10.1172","volume":"10","author":[{"given":"Ali K.","family":"Jaafar","sequence":"first","affiliation":[{"name":"Universit\u00e9 de La R\u00e9union, INSERM, UMR 1188 Diab\u00e8te ath\u00e9rothrombose Th\u00e9rapies R\u00e9union Oc\u00e9an Indien (D\u00e9TROI), Saint-Pierre, La R\u00e9union, France,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aur\u00e9lie","family":"Paulo-Ramos","sequence":"additional","affiliation":[{"name":"Universit\u00e9 de La R\u00e9union, INSERM, UMR 1188 Diab\u00e8te ath\u00e9rothrombose Th\u00e9rapies R\u00e9union Oc\u00e9an Indien (D\u00e9TROI), Saint-Pierre, La R\u00e9union, France,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guillaume","family":"Rastoldo","sequence":"additional","affiliation":[{"name":"Universit\u00e9 de La R\u00e9union, INSERM, UMR 1188 Diab\u00e8te ath\u00e9rothrombose Th\u00e9rapies R\u00e9union Oc\u00e9an Indien (D\u00e9TROI), Saint-Pierre, La R\u00e9union, France,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bryan","family":"Veeren","sequence":"additional","affiliation":[{"name":"Universit\u00e9 de La R\u00e9union, INSERM, UMR 1188 Diab\u00e8te ath\u00e9rothrombose Th\u00e9rapies R\u00e9union Oc\u00e9an Indien (D\u00e9TROI), Saint-Pierre, La R\u00e9union, 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