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REVIEW ARTICLE

Experimental models for investigating hypoxia-inducible factor 1 modulation in neurodegeneration: A comprehensive review

Asma Aktar1* ,  Nowrin Ferdiousi2 ,  Md. Minhazur Rahman3 ,  Amit Kumar Tarafdar1 ,  Kishor Mazumder1,4*
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1 Department of Pharmacy, Faculty of Biological Science and Technology, Jashore University of Science and Technology, Jashore, Khulna , Bangladesh
2 Department of Pharmacy, Faculty of Life Science, Mawlana Bhashani Science and Technology University, Tangail, Dhaka , Bangladesh
3 Department of Pharmacy, Faculty of Science & Engineering, Dhaka International University, Badda, Dhaka , Bangladesh
4 School of Optometry and Vision Science, Faculty of Medicine & Health, University of New South Wales, Sydney, New South Wales , Australia
Received: 17 July 2026 | Revised: 1 September 2026 | Accepted: 15 September 2026 | Published online: 15 October 2026
© 2026 by the Author(s). This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution -Noncommercial 4.0 International License (CC-by the license) ( https://creativecommons.org/licenses/by-nc/4.0/ )
Abstract

Scientific research on modulation of hypoxia-inducible factor 1 (HIF-1) in neurodegeneration has increased considerably; however, selecting appropriate experimental models remains challenging for researchers due to the context-dependent nature of HIF-1 signaling and the diversity of available methodologies. Thus, this review aims to provide a comprehensive overview of the experimental models and methodologies adopted to study HIF-1 modulation in neurodegenerative diseases, focusing on their advantages and limitations as well as suitability for neurodegenerative research contexts. A thorough literature search was conducted across Scopus, PubMed, ScienceDirect, Web of Science, and Google Scholar, covering publications from January 2000 to June 2026. The review encompasses in vitro cellular systems, including primary neuronal and glial cultures, immortalized cell lines such as HT22, SH-SY5Y, and NSC34 cells, organotypic slice cultures, and oxygen–glucose deprivation models. In vivo approaches covered include transgenic mouse models (APP/PS1, 5xFAD, 3xTg-AD, SOD1G93A, microglial Hif1a knockout), chemically induced neurodegeneration models (MPTP, 6-OHDA, rotenone, α-synuclein, 3-nitropropionic acid, acrylonitrile, cobalt chloride, dimethyloxalylglycine), and cerebral ischemia models. Genetic model organisms including Drosophila melanogaster, Caenorhabditis elegans, and Danio rerio are discussed for their unique utility in studying conserved HIF-1 pathways. Moreover, computational approaches are discussed. Major methodological considerations addressed include the balance between experimental design and physiological relevance, cell-type specificity, temporal dynamics of HIF-1 activation, and dose–response relationships for pharmacological modulators. Ultimately, integrating outcomes across multiple experimental systems coupled with rigorous experimental design will be essential for elucidating HIF-1-mediated pathophysiology and facilitating the translation of therapeutic strategies from bench to bedside.

Keywords
Hypoxia-inducible factor 1
Neurodegeneration
Neuronal cell lines
Knockout model
Genetic model
Network pharmacology
Funding
This work received no external funding.
Conflict of interest
The authors declare no conflicts of interest.
References

Abdelsayed, M. (2025). AI-driven polypharmacology in small-molecule drug discovery. International Journal of Molecular Sciences, 26(14), 6996. https://doi.org/10.3390/ijms26146996

 

Ahmed, S., El-Sayed, M. M., Kandeil, M. A., & Khalaf, M. M. (2022). Empagliflozin attenuates neurodegeneration through antioxidant, anti-inflammatory, and modulation of α-synuclein and Parkin levels in rotenone-induced Parkinson’s disease in rats. Saudi Pharmaceutical Journal, 30(6), 863-873. https://doi.org/10.1016/j.jsps.2022.03.005

 

Akki, A. J., Patil, S. A., Hungund, S., Sahana, R., Patil, M. M., Kulkarni, R. V., Raghava Reddy, K., Zameer, F., & Raghu, A. V. (2024). Advances in Parkinson’s disease research–a computational network pharmacological approach. International immunopharmacology, 139, 112758. https://doi.org/10.1016/j.intimp.2024.112758

 

Aktar, A., Ferdiousi, N., Rahman, Md. M., Hossain, Md. S., Islam, F., Roy, D. N., & Mazumder, K. (2026). Mechanistic Insights into the Hypoxia-Inducible Factor-1 Paradox in Alzheimer’s Disease: A Double-Edged Sword in Neurodegeneration. BioChem, 6(3), 23. https://doi.org/10.3390/biochem6030023

 

Al Azad, S., Shetu, T. N., Morshed, A. H., Panah, T., Sultana, S., Ahmed, R., Hasan, S., Siam, N. H., Islam, T., Tabassum, F., Afrin, S., Nafsi, N. N., Nafia, A. K., Sarker, P., Faria, S., &  Riya, F. H. (2025). Extraction, characterization, and dual-phase dosage optimization of selective tumor-suppressing flavonoids for inhibiting cellular proliferation in CRISPR/Cas9-mediated HIF1α-knockout lung adenocarcinoma: integrated in vitro and in silico analysis. Revista Brasileira de Farmacognosia, 35(6), 1231-1246. https://doi.org/10.1007/s43450-025-00690-4

 

Baumann, J., Tsao, C.-C., Huang, S.-F., Gassmann, M., & Ogunshola, O. O. (2021). Astrocyte-specific hypoxia-inducible factor 1 (HIF-1) does not disrupt the endothelial barrier during hypoxia in vitro. Fluids and Barriers of the CNS, 18(1), 13. https://doi.org/10.1186/s12987-021-00247-2

 

Bi, W., Cai, S., Xing, C., Wang, L., & Du, H. (2026). Engineering Mesenchymal Stem Cell Spheroids and Brain Organoids: Advanced 3D Culture Platforms for Neurodegenerative Disease Cell Therapy. Stem Cell Reviews and Reports, 22(4), 1739-1763. https://doi.org/10.1007/s12015-026-11101-z

 

Brishty, S. R., Hossain, M. J., Khandaker, M. U., Faruque, M. R. I., Osman, H., & Rahman, S. M. A. (2021). A comprehensive account on recent progress in pharmacological activities of benzimidazole derivatives. Frontiers in Pharmacology, 12, 762807. https://doi.org/10.3389/fphar.2021.762807

 

Cannon, J. R., Tapias, V., Na, H. M., Honick, A. S., Drolet, R. E., & Greenamyre, J. T. (2009). A highly reproducible rotenone model of Parkinson’s disease. Neurobiology of disease, 34(2), 279-290. https://doi.org/10.1016/j.nbd.2009.01.016

 

Chai, X., Kong, W., Liu, L., Yu, W., Zhang, Z., & Sun, Y. (2014). A viral vector expressing hypoxia-inducible factor 1 alpha inhibits hippocampal neuronal apoptosis. Neural regeneration research, 9(11), 1145-1153. https://doi.org/10.4103/1673-5374.135317

 

Chechneva, O. (2006). Neurodegeneration and neurogenesis in organotypic hippocampal slice cultures after oxygen and glucose deprivation. [PhD dissertation, Otto von Guericke University Magdeburg]. Universitätsbibliothek. https://opendata.uni-halle.de/handle/1981185920/10726

 

Chen, S., Zhang, M., Xing, L., Wang, Y., Xiao, Y., Wu, Y., & Shankar, S. (2015). HIF-1α contributes to proliferation and invasiveness of neuroblastoma cells via SHH signaling. PloS one, 10(3), e0121115. https://doi.org/10.1371/journal.pone.0121115

 

Dong, H., Zhang, X., Duan, Y., He, Y., Zhao, J., Wang, Z., Wang, J., Li, Q., Fan, G., Liu, Z., Shen, C., Zhang, Y., Yu, M., Fei, J., & Huang, F. (2024). Hypoxia inducible factor-1α regulates microglial innate immune memory and the pathology of Parkinson’s disease. Journal of Neuroinflammation, 21(1), 80. https://doi.org/10.1186/s12974-024-03070-2

 

Dong, M., Qian, Y., Geng, Y., Wang, R., Wang, Y., Cai, J., Wang, X., Huang, Y., Liu, Y., Liu, W., Wu, Q., & Shen, Y. (2025). HIF-1α-induced microglia-mediated neuroinflammation is involved in Alzheimer’s disease: Evidence from single-cell transcriptomic analysis. Journal of Alzheimer¡¯s disease, 108(2), 643-660. https://doi.org/10.1177/13872877251378007

 

Eglen, R., & Reisine, T. (2011). Primary cells and stem cells in drug discovery: emerging tools for high-throughput screening. Assay and drug development technologies, 9(2), 108-124. https://doi.org/10.1089/adt.2010.0305

 

Elgindy, A. M., Atwa, A. M., El-Awady, E.-S. E., El-Sayed, N. M., & El-Orabi, N. F. (2025). Neuroprotective effects of candesartan in 3-nitropropionic acid-induced Huntington’s disease: modulation of angiotensin and CREB/BDNF/PGC1-α signaling. Inflammopharmacology, 33(10), 6231-6249. https://doi.org/10.1007/s10787-025-01889-6

 

Elgindy, A. M., El-Awady, E.-S. E., El-Sayed, N. M., El-Orabi, N. F., & Atwa, A. M. (2026). Neuroprotection by canagliflozin in a Huntington’s disease model: role of HIF-1α and PI3K/AKT signaling. Naunyn-Schmiedeberg¡¯s Archives of Pharmacology, 399(6), 8245-8262. https://doi.org/10.1007/s00210-025-04891-5

 

Engelhardt, S. (2014). Facing hypoxia and ischemia: Cell-specific signaling and metabolism at the blood-brain barrier [Doctoral dissertation, University of Zurich]. ZORA (Zurich Open Repository and Archive). https://doi.org/10.5167/UZH-104660

 

Farasati Far, B., Omidvar, K., Heidari, E., Ebrahimi, M., Mohammadi, Y., & Ertas, Y. N. (2025). Neuronal Organoid Engineering and Disease-Focused High-Throughput Neuropharmacology: Advances, Limitations, and Translational Strategies. ACS Pharmacology & Translational Science, 9(1), 1-19. https://doi.org/10.1021/acsptsci.5c00407

 

Fernández-López, D., Martínez-Orgado, J., Casanova, I., Bonet, B., Leza, J. C., Lorenzo, P., Moro, M. Á., & Lizasoain, I. (2005). Immature rat brain slices exposed to oxygen–glucose deprivation as an in vitro model of neonatal hypoxic–ischemic encephalopathy. Journal of neuroscience methods, 145(1-2), 205-212. https://doi.org/10.1016/j.jneumeth.2005.01.005

 

Gonzalez-Rodriguez, P. J., Xiong, F., Li, Y., Zhou, J., & Zhang, L. (2014). Fetal hypoxia increases vulnerability of hypoxic–ischemic brain injury in neonatal rats: Role of glucocorticoid receptors. Neurobiology of disease, 65, 172-179. https://doi.org/10.1016/j.nbd.2014.01.020

 

Gonzalo-Gobernado, R., Moreno-Martínez, L., González, P., Dopazo, X. M., Calvo, A. C., Pidal-Ladrón de Guevara, I., Seisdedos, E., Díaz-Muñoz, R., Mellström, B., Osta, R., & Naranjo, J. R. (2023). Repaglinide Induces ATF6 Processing and Neuroprotection in Transgenic SOD1G93A Mice. International Journal of Molecular Sciences, 24(21), 15783. https://doi.org/10.3390/ijms242115783

 

Grammas, P., Martinez, J., & Miller, B. (2011). Cerebral microvascular endothelium and the pathogenesis of neurodegenerative diseases. Expert reviews in molecular medicine, 13, e19. https://doi.org/10.1017/S1462399411001918

 

Guo, H., Cheng, Y., Wang, C., Wu, J., Zou, Z., Niu, B., Yu, H., Wang, H., & Xu, J. (2017). FFPM, a PDE4 inhibitor, reverses learning and memory deficits in APP/PS1 transgenic mice via cAMP/PKA/CREB signaling and anti-inflammatory effects. Neuropharmacology, 116, 260-269. https://doi.org/10.1016/j.neuropharm.2017.01.004

 

Hu, C.-J., Wang, L.-Y., Chodosh, L. A., Keith, B., & Simon, M. C. (2003). Differential roles of hypoxia-inducible factor 1α (HIF-1α) and HIF-2α in hypoxic gene regulation. Molecular and cellular biology, 23(24), 9361-9374. https://doi.org/10.1128/MCB.23.24.9361-9374.2003

 

Hu, J., Yang, B., Tao, Z., Chen, J., Zhang, X., Wang, S., Xing, G., Ngeng, N. A., Malik, A., Appiah-Kubi, K., Farina, M., Skalny, A. V., Tinkov, A. A., Aschner, M., & Lu, R. (2025). The role of HIF-1α/BNIP3/mitophagy in acrylonitrile-induced neuronal death in HT22 cells and mice: A potential neuroprotection target. Chemico-Biological Interactions, 406, 111327. https://doi.org/10.1016/j.cbi.2024.111327

 

Janowska, J., Ziemka-Nalecz, M., & Sypecka, J. (2025). Inhibition of the HIF-1α Signaling Pathway Promotes Oligodendrocyte Maturation in the In Vitro Model of Perinatal Asphyxia. Molecular neurobiology, 62(12), 15928-15942. https://doi.org/10.1007/s12035-025-05246-0

 

Jaronen, M., Goldsteins, G., & Koistinaho, J. (2014). ER stress and unfolded protein response in amyotrophic lateral sclerosis—a controversial role of protein disulphide isomerase. Frontiers in cellular neuroscience, 8, 402. https://doi.org/10.3389/fncel.2014.00402

 

Jiang, W. I., Cao, Y., Xue, Y., Ji, Y., Winer, B. Y., Chandra, R., Zhang, X. F., Zhang, M., Singhal, N. S., Pierce, J. T., Chen, S., & Ma, D. K. (2025). Suppressing APOE4-induced neural pathologies by targeting the VHL–HIF axis. Proceedings of the National Academy of Sciences, 122(5), e2417515122. https://doi.org/10.1073/pnas.2417515122

 

Johansson, K., Cebula, M., Rengby, O., Dreij, K., Carlström, K. E., Sigmundsson, K., Piehl, F., & Arnér, E. S. J. (2017). Cross talk in HEK293 cells between Nrf2, HIF, and NF-κB activities upon challenges with redox therapeutics characterized with single-cell resolution. Antioxidants & redox signaling, 26(6), 229-246. https://doi.org/10.1089/ars.2015.6419

 

Jung, J., Kim, Y., Cirunduzi, A. C., Yoon, S., Bang, S., & Yang, S. H. (2026). Multi‐Target‐Directed Ligands (MTDLs) as Potential Therapeutic Candidates Targeting Multiple Pathogenic Factor of Alzheimer’s Disease. CNS Neuroscience & Therapeutics, 32(5), e70919. https://doi.org/10.1002/cns.70919

 

Kang, H., Jo, A., Kim, H., Khang, R., Lee, J.-Y., Kim, H., Park, C.-H., Choi, J.-Y., Lee, Y., & Shin, J.-H. (2018). PARIS reprograms glucose metabolism by HIF-1α induction in dopaminergic neurodegeneration. Biochemical and biophysical research communications, 495(4), 2498-2504. https://doi.org/10.1016/j.bbrc.2017.12.147

 

Khan, Z., Michalopoulos, G. K., & Stolz, D. B. (2006). Peroxisomal localization of hypoxia-inducible factors and hypoxia-inducible factor regulatory hydroxylases in primary rat hepatocytes exposed to hypoxia-reoxygenation. The American journal of pathology, 169(4), 1251-1269. https://doi.org/10.2353/ajpath.2006.060360

 

Kupershmidt, L., & Youdim, M. B. (2023). The neuroprotective activities of the novel multi-target iron-chelators in models of Alzheimer’s disease, amyotrophic lateral sclerosis and aging. Cells, 12(5), 763. https://doi.org/10.3390/cells12050763

 

Lei, X., Guo, Q., & Zhang, J. (2012). Mechanistic insights into neurotoxicity induced by anesthetics in the developing brain. International Journal of Molecular Sciences, 13(6), 6772-6799. https://doi.org/10.3390/ijms13066772

 

Li, H., Hua, Q., Cheng, S., Liu, X., Cai, Q., Zhang, J., . . . Liang, C. (2025). The neuroprotect formula: a preventive approach to AD targeting the HIF-1/PI3K-AKT signaling pathway evaluated through in vivo, in vitro, and network pharmacology approaches. Combinatorial Chemistry & High Throughput Screening, 28(6), 1039-1053.  https://doi.org/10.2174/0113862073311518240416070410

 

Li, Q., Han, X., & Wang, J. (2016). Organotypic hippocampal slices as models for stroke and traumatic brain injury. Molecular neurobiology, 53(6), 4226-4237. https://doi.org/10.1007/s12035-015-9362-4

 

Li, X., Cui, X.-X., Chen, Y.-J., Wu, T.-T., Xu, H., Yin, H., & Wu, Y.-C. (2018). Therapeutic potential of a prolyl hydroxylase inhibitor FG-4592 for Parkinson’s diseases in vitro and in vivo: regulation of redox biology and mitochondrial function. Frontiers in Aging Neuroscience, 10, 121. https://doi.org/10.3389/fnagi.2018.00121

 

Lin, T.-K., Huang, C.-R., Lin, K.-J., Hsieh, Y.-H., Chen, S.-D., Lin, Y.-C., Chao, A.-C., & Yang, D.-I. (2024). Potential Roles of Hypoxia-Inducible Factor-1 in Alzheimer’s Disease: Beneficial or Detrimental? Antioxidants, 13(11), 1378. https://doi.org/10.3390/antiox13111378

 

Lin, T.-N., Sun, S.-W., Cheung, W.-M., Li, F., & Chang, C. (2002). Dynamic changes in cerebral blood flow and angiogenesis after transient focal cerebral ischemia in rats: evaluation with serial magnetic resonance imaging. Stroke, 33(12), 2985-2991. https://doi.org/10.1161/01.STR.0000037675.97888.9D

 

Lin, Y., Song, L., Tang, Y., Wang, X., Wu, L., Li, J., Qiu, Q., Dan, X., Wang, W., Cheng, Y., Zhao, H., Li, D., Di, L., Bian, H., Dou, Z., He, L., Wang, Z., Li, X.-Y., Yang, J., & Zhao, G. (2025). Epidemiology of neurological diseases in China: Key insights from the 2024 report of the National Center for Neurological Disorders. Brain Network Disorders, 1(04), 257-264. https://doi.org/10.1016/j.bnd.2025.12.002

 

Liu, X., Chen, S., Zhang, D., Gu, Y., Li, G., Wu, B., Pagán, J. A., Zhang, L., & Li, Y. (2025). Projected Prevalence and Economic Burden of Alzheimer’s Disease and Related Dementias in China: Regional Disparities and Policy Implications. Health Data Science, 5, 0377. https://doi.org/10.34133/hds.0377

 

Ma, Y., Tian, H., Xiao, W., Ma, Y., Su, H., Zhu, L., Jiang, Y., Ge, L., Li, Y., Yuan, M., & Liu, X. (2025). Machine Learning Approaches for Optimizing Drug Combinations in Neurodegenerative Diseases: A Brief Review. ACS omega, 10(48), 57950-57973. https://doi.org/10.1021/acsomega.5c07349

 

Major, D., Dósa, N., Balázs, P., Fekete, M., Pártos, K., Árva, D., Mészáros, Á., Terebessy, A., Tabák, Á. G., & Fazekas-Pongor, V. (2026). Global trends in the incidence and prevalence of Alzheimer’s disease. Advances in Translational Research, 1(1), 21–28. https://doi.org/10.1556/1661.2025.00106

 

Mantri, S., Ghilardi, M. F., Lessard, N., Norcini, M., Di Rocco, A., Wallock, K., Lehr, J., & Okun, M. S. (2025). Proceedings of the world summit on parkinson’s disease. npj Parkinson¡¯s Disease, 11(1), 293. https://doi.org/10.1038/s41531-025-01123-8

 

Maqsood, K., Fatima, M., Naveed, H., Afzal, W., Beg, Z. A., Alhussain, F., Abualait, T., & Bashir, S. (2025). Global and Regional Patterns of Parkinson¡¯s Disease: Temporal Trends, Inequality Gaps, and Projections to 2040 [Preprint]. medRxiv. https://doi.org/10.1101/2025.10.22.25338533

 

March-Diaz, R., Lara-Ureña, N., Romero-Molina, C., Heras-Garvin, A., Ortega-de San Luis, C., Alvarez-Vergara, M. I., Sanchez-Garcia, M. A., Sanchez-Mejias, E., Davila, J. C., Rosales-Nieves, A. E., Forja, C., Navarro, V., Gomez-Arboledas, A., Sanchez-Mico, M. V., Viehweger, A., Gerpe, A., Hodson, E. J., Vizuete, M., Bishop, T., … Pascual, A. (2021). Hypoxia compromises the mitochondrial metabolism of Alzheimer’s disease microglia via HIF1. Nature Aging, 1(4), 385-399. https://doi.org/10.1038/s43587-021-00054-2

 

Mehrabani, M., Nematollahi, M. H., Tarzi, M. E., Juybari, K. B., Abolhassani, M., Sharifi, A. M., Paseban, H., Saravani, M., & Mirzamohammadi, S. (2020). Protective effect of hydralazine on a cellular model of Parkinson’s disease: a possible role of hypoxia-inducible factor (HIF)-1α. Biochemistry and Cell Biology, 98(3), 405-414. https://doi.org/10.1139/bcb-2019-0117

 

Merelli, A., Rodríguez, J. C. G., Folch, J., Regueiro, M. R., Camins, A., & Lazarowski, A. (2018). Understanding the role of hypoxia inducible factor during neurodegeneration for new therapeutics opportunities. Current Neuropharmacology, 16(10), 1484-1498. https://doi.org/10.2174/1570159X16666180110130253

 

Mitroshina, Е. V., Mishchenko, T. A., Shirokova, O. M., Astrakhanova, T. A., Loginova, M. M., Epifanova, E. A., Babaev, A. A., Tarabykin, V. S., & Vedunova, M. V. (2019). Intracellular Neuroprotective Mechanisms in Neuron-Glial Networks Mediated by Glial Cell Line-Derived Neurotrophic Factor. Oxidative Medicine and Cellular Longevity, 2019, 1–15. https://doi.org/10.1155/2019/1036907

 

Muñoz‐Sánchez, J., & Chánez‐Cárdenas, M. E. (2018). The use of cobalt chloride as a chemical hypoxia model. Journal of Applied Toxicology, 39(4), 556–570. https://doi.org/10.1002/jat.3749

 

Nagarajan, S., & Grewal, S. S. (2014). An investigation of nutrient-dependent mRNA translation in Drosophila larvae. Biology open, 3(11), 1020-1031. https://doi.org/10.1242/bio.20149407

 

Newman, M., Nik, H. M., Sutherland, G. T., Hin, N., Kim, W. S., Halliday, G. M., Jayadev, S., Smith, C., Laird, A. S., Lucas, C. W., Kittipassorn, T., Peet, D. J., & Lardelli, M. (2020). Accelerated loss of hypoxia response in zebrafish with familial Alzheimer’s disease-like mutation of presenilin 1. Human molecular genetics, 29(14), 2379-2394. https://doi.org/10.1093/hmg/ddaa119

 

Oblak, A. L., Lin, P. B., Kotredes, K. P., Pandey, R. S., Garceau, D., Williams, H. M., Uyar, A., O’Rourke, R., O’Rourke, S., Ingraham, C., Bednarczyk, D., Belanger, M., Cope, Z. A., Little, G. J., Williams, S.-P. G., Ash, C., Bleckert, A., Ragan, T., Logsdon, B. A., … Lamb, B. T. (2021). Comprehensive evaluation of the 5XFAD mouse model for preclinical testing applications: a MODEL-AD study. Frontiers in Aging Neuroscience, 13, 713726. https://doi.org/10.3389/fnagi.2021.713726

 

Page, S., Raut, S., & Al-Ahmad, A. (2019). Oxygen-glucose deprivation/reoxygenation-induced barrier disruption at the human blood–brain barrier is partially mediated through the HIF-1 pathway. Neuromolecular medicine, 21(4), 414-431. https://doi.org/10.1007/s12017-019-08531-z

 

Pan, E., Gong, X., Chen, Y., & Tang, M. (2026). AI-Driven Network Pharmacology of Traditional Chinese Medicine for Neurodegenerative Diseases. Current Drug Therapy, 21. https://doi.org/10.2174/0115748855403042251118104527

 

Peet, D., & Linke, S. (2006). Regulation of HIF: asparaginyl hydroxylation. In Signalling Pathways in Acute Oxygen Sensing: Novartis Foundation Symposium 272 (pp. 37–53). Wiley. https://doi.org/10.1002/9780470035009.ch5

 

Porel, P., Bala, K., & Aran, K. R. (2025). Exploring the role of HIF-1α on pathogenesis in Alzheimer’s disease and potential therapeutic approaches. Inflammopharmacology, 33(2), 669-678. https://doi.org/10.1007/s10787-024-01585-x

 

Rafeeq, M., Al-Abbasi, F. A., Afzal, M., Saad Alharbi, K., Moglad, E., Al-Qahtani, S. D., A. Bukhari, H., Imam, F., Sayyed, N., & Kazmi, I. (2025). Effects of a Rosiridin against Rotenone-induced Rats Model of Parkinson’s Disease: In-vivo Study and in silico Molecular Modeling. Current Neuropharmacology, 23(9), 1095-1118. https://doi.org/10.2174/011570159X349553250126050134

 

Semenza, G. L. (2004). O2-regulated gene expression: transcriptional control of cardiorespiratory physiology by HIF-1. Journal of Applied Physiology, 96(3), 1173-1177. https://doi.org/10.1152/japplphysiol.00770.2003

 

Serebrovska, Z., Xi, L., Khetsuriani, M., Protsenko, O., Morozova, N., Tolstun, D. A., & Maksymchuk, O. (2025). Utility of Drosophila for studying hypoxia-inducible factor (HIF) in neurodegenerative diseases: Advantages versus limitations. Brain Research, 1867, 149953. https://doi.org/10.1016/j.brainres.2025.149953

 

Sharma, V., Verma, R., & Singh, T. G. (2025). Targeting hypoxia-related pathobiology in Alzheimer’s disease: Strategies for prevention and treatment. Molecular Biology Reports, 52(1), 416. https://doi.org/10.1007/s11033-025-10520-4

 

Singh, A., & Chen, R. (2023). The duration of oxygen and glucose deprivation (OGD) determines the effects of subsequent reperfusion on rat pheochromocytoma (PC12) cells and primary cortical neurons. International Journal of Molecular Sciences, 24(8), 7106. https://doi.org/10.3390/ijms24087106

 

Singh, P., Borkar, M., & Doshi, G. (2026). Network pharmacology approach to unravel the neuroprotective potential of natural products: a narrative review. Molecular Diversity, 30(1), 59-100. https://doi.org/10.1007/s11030-025-11198-3

 

Szklarczyk, D., Nastou, K., Koutrouli, M., Kirsch, R., Mehryary, F., Hachilif, R., Hu, D., Peluso, M. E., Huang, Q., Fang, T., Doncheva, N. T., Pyysalo, S., Bork, P., Jensen, L. J., & von Mering, C. (2025). The STRING database in 2025: protein networks with directionality of regulation. Nucleic acids research, 53(D1), D730-D737. https://doi.org/10.1093/nar/gkae1113

 

Thangwong, P., Tocharus, C., & Tocharus, J. (2025). The bidirectional role of hypoxia-inducible factor 1 alpha in vascular dementia caused by chronic cerebral hypoperfusion. Molecular neurobiology, 62(8), 10398-10413. https://doi.org/10.1007/s12035-025-04914-5

 

van Gijsel-Bonnello, M., Baranger, K., Benech, P., Rivera, S., Khrestchatisky, M., De Reggi, M., & Gharib, B. (2017). Metabolic changes and inflammation in cultured astrocytes from the 5xFAD mouse model of Alzheimer’s disease: Alleviation by pantethine. PloS one, 12(4), e0175369. https://doi.org/10.1371/journal.pone.0175369

 

Van Steenwinckel, J., Bokobza, C., Laforge, M., Shearer, I. K., Miron, V. E., Rua, R., Matta, S. M., Hill‐Yardin, E. L., Fleiss, B., & Gressens, P. (2024). Key roles of glial cells in the encephalopathy of prematurity. Glia, 72(3), 475-503. https://doi.org/10.1002/glia.24474

 

Vrailas-Mortimer, A., del Rivero, T., Mukherjee, S., Nag, S., Gaitanidis, A., Kadas, D., Consoulas, C., Duttaroy, A., & Sanyal, S. (2011). A muscle-specific p38 MAPK/Mef2/MnSOD pathway regulates stress, motor function, and life span in Drosophila. Developmental cell, 21(4), 783-795. https://doi.org/10.1016/j.devcel.2011.09.002

 

Wang, X., Cui, L., & Ji, X. (2022). Cognitive impairment caused by hypoxia: from clinical evidences to molecular mechanisms. Metabolic Brain Disease, 37(1), 51-66. https://doi.org/10.1007/s11011-021-00796-3

 

Xu, R., Wu, C., Zhang, X., Zhang, Q., Yang, Y., Yi, J., Yang, R., & Tao, Y. (2011). Linking hypoxic and oxidative insults to cell death mechanisms in models of ALS. Brain Research, 1372, 133-144. https://doi.org/10.1016/j.brainres.2010.11.056

 

Yang, J., Li, C., Liu, Y., Han, Y., Zhao, H., Luo, S., . . . Sun, L. (2022). Using network pharmacology to explore the mechanism of Danggui-Shaoyao-San in the treatment of diabetic kidney disease. Frontiers in Pharmacology, 13, 832299. https://doi.org/10.3389/fphar.2022.832299

 

Yang, Y., Zhang, J., Liu, H., Wang, J., Xin, J., & Deng, M. (2013). Changes in levels of hypoxia-induced mediators in rat hippocampus during chronic cerebral hypoperfusion. Neurochemical research, 38(11), 2433-2439. https://doi.org/10.1007/s11064-013-1158-1

 

Yeh, S.-H., Hung, J.-J., Gean, P.-W., & Chang, W.-C. (2008). Hypoxia-inducible factor-1α protects cultured cortical neurons from lipopolysaccharide-induced cell death via regulation of NR1 expression. Journal of Neuroscience, 28(52), 14259-14270. https://doi.org/10.1523/JNEUROSCI.4258-08.2008

 

Yenkoyan, K. B., Kotova, M. M., Apukhtin, K. V., Galstyan, D. S., Amstislavskaya, T. G., Strekalova, T., de Abreu, M. S., Chavushyan, V. A., Lim, L. W., Yang, L., Rosemberg, D. B., & Kalueff, A. V. (2025). Experimental modeling of Alzheimer’s disease: Translational lessons from cross‐taxon analyses. Alzheimer¡¯s & Dementia, 21(5), e70273. https://doi.org/10.1002/alz.70273

 

Youdim, M. B., Kupershmidt, L., Amit, T., & Weinreb, O. (2014). Promises of novel multi-target neuroprotective and neurorestorative drugs for Parkinson’s disease. Parkinsonism & related disorders, 20, S132-S136. https://doi.org/10.1016/S1353-8020(13)70032-4

 

Zhang, J.-B., Wan, X.-J., Duan, W.-X., Dai, X.-Q., Xia, D., Fu, X., Hu, L.-F., Wang, F., & Liu, C.-F. (2024). Circadian disruption promotes the neurotoxicity of oligomeric alpha-synuclein in mice. npj Parkinson¡¯s Disease, 10(1), 179. https://doi.org/10.1038/s41531-024-00798-9

 

Zhang, W., Ren, J., Ding, L., Zheng, S., Ma, R., Zhang, M., Liu, Y., Liang, R., & Zhang, Y. (2024). Nanotherapeutic Approaches of Interleukin‐3 to Clear the α‐Synuclein Pathology in Mouse Models of Parkinson’s Disease. Advanced Science, 11(42), 2405364. https://doi.org/10.1002/advs.202405364

 

Zhang, X., Alshakhshir, N., & Zhao, L. (2021). Glycolytic metabolism, brain resilience, and Alzheimer’s disease. Frontiers in Neuroscience, 15, 662242. https://doi.org/10.3389/fnins.2021.662242

 

Zhang, Z., Yan, J., Chang, Y., ShiDu Yan, S., & Shi, H. (2011). Hypoxia inducible factor-1 as a target for neurodegenerative diseases. Current medicinal chemistry, 18(28), 4335-4343. https://doi.org/10.2174/092986711797200426

 

Zheng, F., Chen, J., Zhang, X., Wang, Z., Chen, J., Lin, X., Huang, H., Fu, W., Liang, J., Wu, W., Li, B., Yao, H., Hu, H., & Song, E. (2021). The HIF-1α antisense long non-coding RNA drives a positive feedback loop of HIF-1α mediated transactivation and glycolysis. Nature communications, 12(1), 1341. https://doi.org/10.1038/s41467-021-21535-3

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