{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T17:30:13Z","timestamp":1788888613525,"version":"build-2803163510"},"reference-count":65,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2017,4,26]],"date-time":"2017-04-26T00:00:00Z","timestamp":1493164800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Neuropathology Appl Neurobio"],"published-print":{"date-parts":[[2018,6]]},"abstract":"<jats:sec><jats:title>Aims<\/jats:title><jats:p>X\u2010linked adrenoleukodystrophy (X\u2010ALD) is a genetic white matter disorder in which demyelination occurs due to accumulation of very long\u2010chain fatty acids. Inflammation in the brain white matter is a hallmark of the pathology of cerebral X\u2010ALD, but the underlying pathogenic mechanisms are still largely unknown. In other inflammatory demyelinating disorders, such as multiple sclerosis, the expression of heat shock proteins (HSPs) in combination with interferon\u2010\u03b3 (IFN\u2010\u03b3) has been suggested to play a prominent role in the initiation of demyelination and inflammation. We therefore investigated these pathways in X\u2010ALD lesions.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>By immunohistochemistry, we examined the expression of small HSPs (HSPB1, HSPB5, HSPB6, HSPB8) and higher molecular weight HSPs (HSPA, HSPD1), and the expression of elements of the IFN\u2010\u03b3 pathway on autopsy material of five patients with X\u2010ALD.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The expression of the larger HSPs, HSPA and HSPD1, as well as small HSPs is increased in X\u2010ALD lesions compared with normal\u2010appearing white matter. Such upregulation can already be detected before demyelination and inflammation occur, and it is predominant in astrocytes. The IFN\u2010\u03b3 pathway does not seem to play a leading role in the observed inflammation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>The finding that astrocytes show signs of cellular stress before demyelination suggests that they play a major role early in the pathogenesis of cerebral X\u2010ALD, and may therefore be involved in the initiation of inflammation and demyelination.<\/jats:p><\/jats:sec>","DOI":"10.1111\/nan.12399","type":"journal-article","created":{"date-parts":[[2017,3,20]],"date-time":"2017-03-20T14:26:54Z","timestamp":1490020014000},"page":"363-376","source":"Crossref","is-referenced-by-count":29,"title":["Heat shock protein expression in cerebral X\u2010linked adrenoleukodystrophy reveals astrocyte stress prior to myelin loss"],"prefix":"10.1111","volume":"44","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4455-1432","authenticated-orcid":false,"given":"A. 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