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peptide and hyperphosphorylated tau protein, respectively. The excessive production of reactive oxygen species (ROS) and neuroinflammation are crucial contributing factors to the pathological mechanisms of AD. Hypoxia-inducible factor-1 (HIF-1) is a transcription factor critical for tissue adaption to low-oxygen tension. Growing evidence has suggested HIF-1 as a potential therapeutic target for AD; conversely, other experimental findings indicate that HIF-1 induction contributes to AD pathogenesis. These previous findings thus point to the complex, even contradictory, roles of HIF-1 in AD. In this review, we first introduce the general pathogenic mechanisms of AD as well as the potential pathophysiological roles of HIF-1 in cancer, immunity, and oxidative stress. Based on current experimental evidence in the literature, we then discuss the possible beneficial as well as detrimental mechanisms of HIF-1 in AD; these sections also include the summaries of multiple chemical reagents and proteins that have been shown to exert beneficial effects in AD via either the induction or inhibition of HIF-1.<\/jats:p>","DOI":"10.3390\/antiox13111378","type":"journal-article","created":{"date-parts":[[2024,11,11]],"date-time":"2024-11-11T08:01:27Z","timestamp":1731312087000},"page":"1378","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":27,"title":["Potential Roles of Hypoxia-Inducible Factor-1 in Alzheimer\u2019s Disease: Beneficial or Detrimental?"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6656-1319","authenticated-orcid":false,"given":"Tsu-Kung","family":"Lin","sequence":"first","affiliation":[{"name":"Department of Neurology, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 833401, Taiwan"},{"name":"College of Medicine, Chang Gung University, Taoyuan 333323, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chi-Ren","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Neurology, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 833401, Taiwan"},{"name":"College of Medicine, Chang Gung University, Taoyuan 333323, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kai-Jung","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Family Medicine, National Taiwan University Hospital, Taipei 100225, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi-Heng","family":"Hsieh","sequence":"additional","affiliation":[{"name":"Institute of Brain Science, National Yang Ming Chiao Tung University, Taipei 112304, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7879-2579","authenticated-orcid":false,"given":"Shang-Der","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Neurology, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 833401, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi-Chun","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Neurology, Taipei City Hospital Renai Branch, Taipei 106243, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1230-9622","authenticated-orcid":false,"given":"A-Ching","family":"Chao","sequence":"additional","affiliation":[{"name":"Department of Neurology, Kaohsiung Medical University Hospital, Kaohsiung 807377, Taiwan"},{"name":"Department of Neurology, College of Medicine, Kaohsiung Medical University, Kaohsiung 807378, Taiwan"},{"name":"Department of Sports Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 807378, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5544-7561","authenticated-orcid":false,"given":"Ding-I","family":"Yang","sequence":"additional","affiliation":[{"name":"Institute of Brain Science, National Yang Ming Chiao Tung University, Taipei 112304, Taiwan"},{"name":"Brain Research Center, National Yang Ming Chiao Tung University, Taipei 112304, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,11,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Dugger, B.N., and Dickson, D.W. 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