The DOI matches its Crossref record; 66 of the 66 references it cites were found in a registry or an index.
Iron dyshomeostasis, lipid peroxidation and perturbed expression of cystine/glutamate antiporter in Alzheimer’s disease: Evidence of ferroptosis
Open accessAbstract
Iron dyshomeostasis is implicated in Alzheimer’s disease (AD) alongside β-amyloid and tau pathologies. Despite the recent discovery of ferroptosis, an iron-dependent form cell death, hitherto, in vivo evidence of ferroptosis in AD is lacking. The present study uniquely adopts an integrated multi-disciplinary approach, combining protein (Western blot) and elemental analysis (total reflection X-ray fluorescence) with metabolomics (1H nuclear magnetic resonance spectroscopy) to identify iron dyshomeostasis and ferroptosis, and possible novel interactions with metabolic dysfunction in age-matched male cognitively normal (CN) and AD post-mortem brain tissue (n = 7/group). Statistical analysis was used to compute differences between CN and AD, and to examine associations between proteins, elements and/or metabolites. Iron dyshomeostasis with elevated levels of ferritin, in the absence of increased elemental iron, was observed in AD. Moreover, AD was characterised by enhanced expression of the light-chain subunit of the cystine/glutamate transporter (xCT) and lipid peroxidation, reminiscent of ferroptosis, alongside an augmented excitatory glutamate to inhibitory GABA ratio. Protein, element and metabolite associations also greatly differed between CN and AD suggesting widespread metabolic dysregulation in AD. We demonstrate iron dyshomeostasis, upregulated xCT (impaired glutathione metabolism) and lipid peroxidation in AD, suggesting anti-ferroptotic therapies may be efficacious in AD.
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Cites
Ferroptosis: An Iron-Dependent Form of Nonapoptotic Cell Death
Dixon, S. J., Lemberg, K. M., Lamprecht, M. R., Skouta, R., Zaitsev, E. M., Gleason, C. E., Patel, D. N., Bauer, A. J., Cantley, A. M., Yang, W. S., et al. (2012) · Cell · doi:10.1016/j.cell.2012.03.042 · Cited by 18,691
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Ferroptosis: A Regulated Cell Death Nexus Linking Metabolism, Redox Biology, and Disease
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ACSL4 dictates ferroptosis sensitivity by shaping cellular lipid composition
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Oxidized arachidonic and adrenic PEs navigate cells to ferroptosis
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Peroxidation of polyunsaturated fatty acids by lipoxygenases drives ferroptosis
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Glutaminolysis and transferrin regulate ferroptosis
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The role of iron in brain ageing and neurodegenerative disorders
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Cited by
Iron Homeostasis and Ferroptosis in Human Diseases: Mechanisms and Therapeutic Prospects
Ru, Q., Li, Y., Chen, L., Wu, Y., Min, J., & Wang, F. (2024) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-024-01969-z · Cited by 724
GPX4: The hub of lipid oxidation, ferroptosis, disease and treatment
Liu, Y., Wan, Y., Jiang, Y., Zhang, L., & Cheng, W. (2023) · Biochimica et Biophysica Acta (BBA) - Reviews on Cancer · doi:10.1016/j.bbcan.2023.188890 · Cited by 528
Molecular mechanisms of ferroptosis and their involvement in brain diseases
Costa, I., Barbosa, D. J., Benfeito, S., Silva, V., Chavarria, D., Borges, F., Remião, F., & Silva, R. (2023) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2023.108373 · Cited by 402
Oxidative Stress: Signaling Pathways, Biological Functions, and Disease
Liu, S., Liu, J., Wang, Y., Deng, F., & Deng, Z. (2025) · MedComm · doi:10.1002/mco2.70268 · Cited by 359
Chemistry and biology of ferritin
Plays, M., Müller, S., & Rodriguez, R. (2021) · Metallomics · doi:10.1093/mtomcs/mfab021 · Cited by 232
Metadata
- Authors
- Ashraf, A., Jeandriens, J., Parkes, H. G., & So, P.-W.
- Venue
- Redox Biology
- Publisher
- Elsevier BV
- Published
- 2020-05
- Volume
- 32
- Pages
- 101494
- ISSN
- 2213-2317 (ISSN-L)
- OpenAlex
- W3010188616
- Cited by
- 300
- References
- 66
- FWCI
- 16.72
- Type
- journal article
- Language
- en
- Open access
- gold
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- Ashraf, A., Jeandriens, J., Parkes, H. G., & So, P.-W. (2020). Iron dyshomeostasis, lipid peroxidation and perturbed expression of cystine/glutamate antiporter in Alzheimer’s disease: Evidence of ferroptosis. Redox Biology. https://doi.org/10.1016/j.redox.2020.101494
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Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.
