The Regulation of Glucose Metabolism by HIF-1 Mediates a Neuroprotective Response to Amyloid Beta Peptide
Open accessAbstract
It is frequently argued that both amyloid beta (Abeta) and oxidative stress are involved in the pathogenesis of Alzheimer's disease (AD). We show here that clonal nerve cell lines and primary cortical neurons that are resistant to Abeta toxicity have an enhanced flux of glucose through both the glycolytic pathway and the hexose monophosphate shunt. AD brain also has increased enzymatic activities in both pathways relative to age-matched controls. The Abeta-induced changes in glucose metabolism are due to the activation of the transcription factor hypoxia inducible factor 1 (HIF-1). As a result of Abeta-induced changes in glucose metabolism, Abeta-resistant cells are more readily killed by glucose starvation and by classes of antipsychotic drugs that inhibit glucose uptake.
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The authors' results support the increase in glycolytic enzymes observed in frontal cortex lysate of AD patients and in glial cells after treatment with AD plasma.
“These results support the increase in glycolytic enzymes that has been observed in the frontal cortex lysate of AD patients as well as glial cells after treatment with AD plasma [25,26].”
From APOE4 Increases Energy Metabolism in APOE-Isogenic iPSC-Derived Neurons (2024) · cites this paper as [25]
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- Authors
- Soucek, T., Cumming, R., Dargusch, R., Maher, P., & Schubert, D.
- Affiliations
- Salk Institute for Biological Studies (US)
- Scripps Research Institute (US)
- Corresponding author
- Schubert, David
- Venue
- Neuron
- Publisher
- Elsevier BV
- Published
- 2003-07
- Volume
- 39
- Issue
- 1
- Pages
- 43-56
- ISSN
- 0896-6273 (ISSN-L)
- OpenAlex
- W2092800106
- Cited by
- 258
- References
- 3
- Citations by year
- 2026: 5 · 2025: 11 · 2024: 13 · 2023: 16 · 2022: 12 · 2021: 12 · 2020: 11 · 2019: 9 · 2018: 9 · 2017: 20 · 2016: 8 · 2015: 10 · 2014: 15 · 2013: 10 · 2012: 17
- FWCI
- 3.97
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Neuron (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute on Aging (P50AG005142)
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Hypoxia, and Metabolism
- Keywords
- amyloid-beta, HIF-1, glucose metabolism, neuroprotection, Alzheimer's disease, glycolysis, pentose phosphate pathway, oxidative stress, glucose deprivation, antipsychotic drugs, cortical neurons, hypoxia
- MeSH terms
- Alzheimer Disease, Animals, Brain, DNA-Binding Proteins, Drug Resistance, Glucose, Humans, Neurons, Nuclear Proteins, Pentose Phosphate Pathway, Antipsychotic Agents, Transcription Factors, Up-Regulation, Amyloid beta-Peptides, PC12 Cells, Reactive Oxygen Species, Neuroprotective Agents, Mice, Rats, Hypoxia-Inducible Factor 1, Hypoxia-Inducible Factor 1, alpha Subunit
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