{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T02:50:09Z","timestamp":1791859809378,"version":"4.3.4"},"reference-count":92,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2021,10,29]],"date-time":"2021-10-29T00:00:00Z","timestamp":1635465600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J of Neuroscience Research"],"published-print":{"date-parts":[[2021,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    X\u2010linked adrenoleukodystrophy (X\u2010ALD) is a phenotypically heterogeneous disorder involving defective peroxisomal \u03b2\u2010oxidation of very long\u2010chain fatty acids (VLCFAs), due to mutation in the\n                    <jats:italic>ABCD1<\/jats:italic>\n                    gene. X\u2010ALD is the most common peroxisomal inborn error of metabolism and confers a high degree of morbidity and mortality. Remarkably, a subset of patients exhibit a cerebral form with inflammatory invasion of the central nervous system and extensive demyelination, while in others only dying\u2010back axonopathy or even isolated adrenal insufficiency is seen, without genotype\u2013phenotype correlation. X\u2010ALD's biochemical signature is marked elevation of VLCFAs in blood, a finding that has been utilized for massive newborn screening for early diagnosis. Investigational gene therapy approaches hold promises for improved outcomes. However, the pathophysiological mechanisms of the disease remain poorly understood, limiting investigation of targeted therapeutic options. Animal models for the disease recapitulate the biochemical signature of VLCFA accumulation and demonstrate mitochondrially generated reactive oxygen species, oxidative damage, increased glial death, and axonal damage. Most strikingly, however, cerebral invasion of leukocytes and demyelination were not observed in any animal model for X\u2010ALD, reflecting upon pathological processes that are yet to be discovered. This review summarizes the current disease models in animals, the lessons learned from these models, and the gaps that remained to be filled in order to assist in therapeutic investigations for ALD.\n                  <\/jats:p>","DOI":"10.1002\/jnr.24953","type":"journal-article","created":{"date-parts":[[2021,10,30]],"date-time":"2021-10-30T00:54:36Z","timestamp":1635555276000},"page":"3170-3181","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":27,"title":["ABCD1 and X\u2010linked adrenoleukodystrophy: A disease with a markedly variable phenotype showing conserved neurobiology in animal models"],"prefix":"10.1002","volume":"99","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4513-8292","authenticated-orcid":false,"given":"Joshua","family":"Manor","sequence":"first","affiliation":[{"name":"Department of Molecular and Human Genetics Baylor College of Medicine  Houston Texas USA"},{"name":"Jan and Dan Duncan Neurological Research Institute at Texas Children\u2019s Hospital  Houston Texas USA"},{"name":"Texas Children's Hospital  Houston Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hyunglok","family":"Chung","sequence":"additional","affiliation":[{"name":"Department of Molecular and Human Genetics Baylor College of Medicine  Houston Texas USA"},{"name":"Jan and Dan Duncan Neurological Research Institute at Texas Children\u2019s Hospital  Houston Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pranjali K.","family":"Bhagwat","sequence":"additional","affiliation":[{"name":"Department of Molecular and Human Genetics Baylor College of Medicine  Houston Texas USA"},{"name":"Jan and Dan Duncan Neurological Research Institute at Texas Children\u2019s Hospital  Houston Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5245-5910","authenticated-orcid":false,"given":"Michael F.","family":"Wangler","sequence":"additional","affiliation":[{"name":"Department of Molecular and Human Genetics Baylor College of Medicine  Houston Texas USA"},{"name":"Jan and Dan Duncan Neurological Research Institute at Texas Children\u2019s Hospital  Houston Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2021,10,29]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00160485"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2019.09.013"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroscience.2012.03.058"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biochi.2013.11.023"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/glia.24042"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/glia.23598"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2020.04.001"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2020.02.021"},{"key":"e_1_2_10_10_1","volume-title":"The cell: A molecular approach","author":"Cooper G. 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