{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T03:14:20Z","timestamp":1791947660875,"version":"4.3.4"},"reference-count":32,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2019,8,2]],"date-time":"2019-08-02T00:00:00Z","timestamp":1564704000000},"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":["Journal of Neurochemistry"],"published-print":{"date-parts":[[2019,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Hypoxia\u2010inducible factor (HIF\u20101) as the primary factor mediating gene\u2010dependent cellular responses to hypoxia represents an attractive target for the therapeutic interventions. The current Editorial comments on an as yet underestimated facet of HIF\u20101\u2013related research. The activity of HIF\u20101 is being regulated by the availability of its \u03b1\u2010subunit HIF\u20101\u03b1, which undergoes quick degradation. The process of degradation is initiated by prolyl 4\u2010hydroxylase (PHD). PHD is an oxygen\u2010dependent enzyme and therefore is inactivated in hypoxia, in turn resulting in HIF\u20101\u03b1 stabilization, its dimerization with HIF\u20101\u03b2 subunit thereby producing the transcriptionally active factor. It has been suggested that pharmacological inhibition of PHD activity might give the same results. Indeed, a large body of evidence on beneficial effects of PHD inhibitors has been accumulated in multiple laboratory and clinical trials. In addition to them, a paper by Li and colleagues published in this issue of <jats:italic>Journal of Neurochemistry<\/jats:italic> also reports that inhibition of PHD by adaptaquin reduces hypoxic\u2010ischemic brain injury in a neonatal mouse model. When dissecting the underlying molecular mechanisms, Li and colleagues surprisingly found that the observed effects appear to be independent of HIF\u20101. These findings draw attention back to the question about possible HIF\u20101 effects independent of PHD inhibitors, which has been raised several years ago but has not received sufficient attention so far, and is being discussed in this Editorial. One of the possible mechanisms might be ascribed to the ferroptosis pathway affected by PHD inhibitors but this question needs further careful studies, as well as clarification of other mechanisms possibly involved. Even if they represent a prospective therapeutic strategy, the lack of current knowledge about endogenous targets of PHD inhibitors, except for PHD, calls for a careful and balanced approach toward their clinical use.<\/jats:p><jats:p>\n<jats:boxed-text content-type=\"graphic\" position=\"anchor\"><jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" mimetype=\"image\/png\" position=\"anchor\" specific-use=\"enlarged-web-image\" xlink:href=\"graphic\/jnc14822-fig-0001-m.png\"><jats:alt-text>image<\/jats:alt-text><\/jats:graphic><\/jats:boxed-text>\n<\/jats:p>","DOI":"10.1111\/jnc.14822","type":"journal-article","created":{"date-parts":[[2019,8,2]],"date-time":"2019-08-02T12:22:37Z","timestamp":1564748557000},"page":"645-647","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Neuroprotective action of PHD inhibitors is predominantly 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