{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T02:31:54Z","timestamp":1781058714471,"version":"3.54.1"},"reference-count":236,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2023,12,23]],"date-time":"2023-12-23T00:00:00Z","timestamp":1703289600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000864","name":"Michael J. Fox Foundation for Parkinson's Research","doi-asserted-by":"publisher","award":["019201"],"award-info":[{"award-number":["019201"]}],"id":[{"id":"10.13039\/100000864","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["movementdisorders.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Movement Disorders"],"published-print":{"date-parts":[[2024,2]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Parkinson's disease (PD) is a progressive neurodegenerative disorder for which only symptomatic treatments are available. Both preclinical and clinical studies suggest that moderate hypoxia induces evolutionarily conserved adaptive mechanisms that enhance neuronal viability and survival. Therefore, targeting the hypoxia response pathway might provide neuroprotection by ameliorating the deleterious effects of mitochondrial dysfunction and oxidative stress, which underlie neurodegeneration in PD. Here, we review experimental studies regarding the link between PD pathophysiology and neurophysiological adaptations to hypoxia. We highlight the mechanistic differences between the rescuing effects of chronic hypoxia in neurodegeneration and short\u2010term moderate hypoxia to improve neuronal resilience, termed \u201chypoxic conditioning\u201d. Moreover, we interpret these preclinical observations regarding the pharmacological targeting of the hypoxia response pathway. Finally, we discuss controversies with respect to the differential effects of hypoxia response pathway activation across the PD spectrum, as well as intervention dosing in hypoxic conditioning and potential harmful effects of such interventions. We recommend that initial clinical studies in PD should focus on the safety, physiological responses, and mechanisms of hypoxic conditioning, as well as on repurposing of existing pharmacological compounds. \u00a9 2023 International Parkinson and Movement Disorder Society.<\/jats:p>","DOI":"10.1002\/mds.29688","type":"journal-article","created":{"date-parts":[[2023,12,23]],"date-time":"2023-12-23T03:25:35Z","timestamp":1703301935000},"page":"273-293","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["The Hypoxia Response Pathway: A Potential Intervention Target in Parkinson's Disease?"],"prefix":"10.1002","volume":"39","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6290-5882","authenticated-orcid":false,"given":"Jules M.","family":"Janssen Daalen","sequence":"first","affiliation":[{"name":"Center of Expertise for Parkinson and Movement Disorders, Department of Neurology, Donders Institute for Brain, Cognition and Behavior, Nijmegen, the Netherlands  Nijmegen The Netherlands"},{"name":"Department of Neurology Radboud University Medical Center, Donders Institute for Brain, Cognition and Behavior  Nijmegen The Netherlands"},{"name":"Department of Physiology Radboud University Medical Center  Nijmegen The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Werner J.H.","family":"Koopman","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Amalia Children's Hospital Radboud Institute for Molecular Life Sciences, Radboud University Medical Center  Nijmegen The Netherlands"},{"name":"Radboud Center for Mitochondrial Medicine Radboud University Medical Center  Nijmegen The Netherlands"},{"name":"Human and Animal Physiology Wageningen University  Wageningen The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christiaan G.J.","family":"Saris","sequence":"additional","affiliation":[{"name":"Department of Neurology Radboud 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