{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,10]],"date-time":"2026-07-10T01:45:37Z","timestamp":1783647937308,"version":"3.55.0"},"reference-count":51,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2022,6,4]],"date-time":"2022-06-04T00:00:00Z","timestamp":1654300800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"NINDS","award":["R01 NS072446"],"award-info":[{"award-number":["R01 NS072446"]}]},{"name":"NINDS","award":["R01 NS082331"],"award-info":[{"award-number":["R01 NS082331"]}]},{"name":"NINDS","award":["ELA 2019-012I2"],"award-info":[{"award-number":["ELA 2019-012I2"]}]},{"name":"the European Leukodystrophy Association","award":["R01 NS072446"],"award-info":[{"award-number":["R01 NS072446"]}]},{"name":"the European Leukodystrophy Association","award":["R01 NS082331"],"award-info":[{"award-number":["R01 NS082331"]}]},{"name":"the European Leukodystrophy Association","award":["ELA 2019-012I2"],"award-info":[{"award-number":["ELA 2019-012I2"]}]},{"name":"the Arrivederci Foundation","award":["R01 NS072446"],"award-info":[{"award-number":["R01 NS072446"]}]},{"name":"the Arrivederci Foundation","award":["R01 NS082331"],"award-info":[{"award-number":["R01 NS082331"]}]},{"name":"the Arrivederci Foundation","award":["ELA 2019-012I2"],"award-info":[{"award-number":["ELA 2019-012I2"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Mutations in the peroxisomal half-transporter ABCD1 cause X-linked adrenoleukodystrophy, resulting in elevated very long-chain fatty acids (VLCFA), progressive neurodegeneration and an associated pain syndrome that is poorly understood. In the nervous system of mice, we found ABCD1 expression to be highest in dorsal root ganglia (DRG), with satellite glial cells (SGCs) displaying higher expression than neurons. We subsequently examined sensory behavior and DRG pathophysiology in mice deficient in ABCD1 compared to wild-type mice. Beginning at 8 months of age, Abcd1\u2212\/y mice developed persistent mechanical allodynia. DRG had a greater number of IB4-positive nociceptive neurons expressing PIEZO2, the mechanosensitive ion channel. Blocking PIEZO2 partially rescued the mechanical allodynia. Beyond affecting neurons, ABCD1 deficiency impacted SGCs, as demonstrated by high levels of VLCFA, increased glial fibrillary acidic protein (GFAP), as well as genes disrupting neuron-SGC connectivity. These findings suggest that lack of the peroxisomal half-transporter ABCD1 leads to PIEZO2-mediated mechanical allodynia as well as SGC dysfunction. Given the known supportive role of SGCs to neurons, this elucidates a novel mechanism underlying pain in X-linked adrenoleukodystrophy.<\/jats:p>","DOI":"10.3390\/cells11111842","type":"journal-article","created":{"date-parts":[[2022,6,4]],"date-time":"2022-06-04T09:42:32Z","timestamp":1654335752000},"page":"1842","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Peroxisome Metabolism Contributes to PIEZO2-Mediated Mechanical Allodynia"],"prefix":"10.3390","volume":"11","author":[{"given":"Yi","family":"Gong","sequence":"first","affiliation":[{"name":"Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fiza","family":"Laheji","sequence":"additional","affiliation":[{"name":"Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Berenson","sequence":"additional","affiliation":[{"name":"Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0942-9631","authenticated-orcid":false,"given":"April","family":"Qian","sequence":"additional","affiliation":[{"name":"Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sang-O","family":"Park","sequence":"additional","affiliation":[{"name":"Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rene","family":"Kok","sequence":"additional","affiliation":[{"name":"Laboratory Genetic Metabolic Diseases, Department of Clinical Chemistry, Amsterdam University Medical Center, Amsterdam Gastroenterology Endocrinology Metabolism, University of Amsterdam, 1105 Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"Selig","sequence":"additional","affiliation":[{"name":"Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3482-8247","authenticated-orcid":false,"given":"Ryan","family":"Hahn","sequence":"additional","affiliation":[{"name":"Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Reza","family":"Sadjadi","sequence":"additional","affiliation":[{"name":"Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2023-064X","authenticated-orcid":false,"given":"Stephan","family":"Kemp","sequence":"additional","affiliation":[{"name":"Laboratory Genetic Metabolic Diseases, Department of Clinical Chemistry, Amsterdam University Medical Center, Amsterdam Gastroenterology Endocrinology Metabolism, University of Amsterdam, 1105 Amsterdam, The Netherlands"},{"name":"Department of Pediatric Neurology, Emma Children\u2019s Hospital, Amsterdam University Medical Center, Amsterdam Neuroscience, University of Amsterdam, 1105 Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Florian","family":"Eichler","sequence":"additional","affiliation":[{"name":"Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,6,4]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"334","DOI":"10.1093\/brain\/awy299","article-title":"Progression of myelopathy in males with adrenoleukodystrophy: Towards clinical trial readiness","volume":"142","author":"Huffnagel","year":"2019","journal-title":"Brain"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1186\/s13023-019-1008-6","article-title":"Disease progression in women with X-linked adrenoleukodystrophy is slow","volume":"14","author":"Huffnagel","year":"2019","journal-title":"Orphanet J. 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