Potential Roles of Hypoxia-Inducible Factor-1 in Alzheimer’s Disease: Beneficial or Detrimental?
The major pathological characteristics of Alzheimer’s disease (AD) include senile plaques and neurofibrillary tangles (NFTs), which are mainly composed of aggregated amyloid-beta (Aβ) peptide and hyperphosphorylated tau protein, respectively. The excessive production of reactive oxygen species (ROS)...
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2024-11-01
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| Series: | Antioxidants |
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| author | Tsu-Kung Lin Chi-Ren Huang Kai-Jung Lin Yi-Heng Hsieh Shang-Der Chen Yi-Chun Lin A-Ching Chao Ding-I Yang |
| author_facet | Tsu-Kung Lin Chi-Ren Huang Kai-Jung Lin Yi-Heng Hsieh Shang-Der Chen Yi-Chun Lin A-Ching Chao Ding-I Yang |
| author_sort | Tsu-Kung Lin |
| collection | DOAJ |
| description | The major pathological characteristics of Alzheimer’s disease (AD) include senile plaques and neurofibrillary tangles (NFTs), which are mainly composed of aggregated amyloid-beta (Aβ) 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. |
| format | Article |
| id | doaj-art-3ec10bfd3daa46cd8efc27baa4f42ee8 |
| institution | OA Journals |
| issn | 2076-3921 |
| language | English |
| publishDate | 2024-11-01 |
| publisher | MDPI AG |
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| series | Antioxidants |
| spelling | doaj-art-3ec10bfd3daa46cd8efc27baa4f42ee82025-08-20T02:08:00ZengMDPI AGAntioxidants2076-39212024-11-011311137810.3390/antiox13111378Potential Roles of Hypoxia-Inducible Factor-1 in Alzheimer’s Disease: Beneficial or Detrimental?Tsu-Kung Lin0Chi-Ren Huang1Kai-Jung Lin2Yi-Heng Hsieh3Shang-Der Chen4Yi-Chun Lin5A-Ching Chao6Ding-I Yang7Department of Neurology, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 833401, TaiwanDepartment of Neurology, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 833401, TaiwanDepartment of Family Medicine, National Taiwan University Hospital, Taipei 100225, TaiwanInstitute of Brain Science, National Yang Ming Chiao Tung University, Taipei 112304, TaiwanDepartment of Neurology, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 833401, TaiwanDepartment of Neurology, Taipei City Hospital Renai Branch, Taipei 106243, TaiwanDepartment of Neurology, Kaohsiung Medical University Hospital, Kaohsiung 807377, TaiwanInstitute of Brain Science, National Yang Ming Chiao Tung University, Taipei 112304, TaiwanThe major pathological characteristics of Alzheimer’s disease (AD) include senile plaques and neurofibrillary tangles (NFTs), which are mainly composed of aggregated amyloid-beta (Aβ) 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.https://www.mdpi.com/2076-3921/13/11/1378amyloid-beta peptide (Aβ)amyloid precursor protein (APP)microglianeurofibrillary tangle (NFT)neuroinflammationoxidative stress |
| spellingShingle | Tsu-Kung Lin Chi-Ren Huang Kai-Jung Lin Yi-Heng Hsieh Shang-Der Chen Yi-Chun Lin A-Ching Chao Ding-I Yang Potential Roles of Hypoxia-Inducible Factor-1 in Alzheimer’s Disease: Beneficial or Detrimental? Antioxidants amyloid-beta peptide (Aβ) amyloid precursor protein (APP) microglia neurofibrillary tangle (NFT) neuroinflammation oxidative stress |
| title | Potential Roles of Hypoxia-Inducible Factor-1 in Alzheimer’s Disease: Beneficial or Detrimental? |
| title_full | Potential Roles of Hypoxia-Inducible Factor-1 in Alzheimer’s Disease: Beneficial or Detrimental? |
| title_fullStr | Potential Roles of Hypoxia-Inducible Factor-1 in Alzheimer’s Disease: Beneficial or Detrimental? |
| title_full_unstemmed | Potential Roles of Hypoxia-Inducible Factor-1 in Alzheimer’s Disease: Beneficial or Detrimental? |
| title_short | Potential Roles of Hypoxia-Inducible Factor-1 in Alzheimer’s Disease: Beneficial or Detrimental? |
| title_sort | potential roles of hypoxia inducible factor 1 in alzheimer s disease beneficial or detrimental |
| topic | amyloid-beta peptide (Aβ) amyloid precursor protein (APP) microglia neurofibrillary tangle (NFT) neuroinflammation oxidative stress |
| url | https://www.mdpi.com/2076-3921/13/11/1378 |
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