Ferroptosis-related mechanisms in prion diseases provide insights into neurodegeneration and reveal therapeutic implications.

Overview

Authors: Mohammed Zayed^1,2,3, Hilal Tayara⁴, Byung-Hoon Jeong^1,2

ORCID iDs: Mohammed Zayed, Byung-Hoon Jeong

Korea Zoonosis Research Institute, Jeonbuk National University, Iksan, 54531, Republic of Korea
Department of Bioactive Material Sciences, Jeonbuk National University, Jeonju, 54896, Republic of Korea
Department of Surgery, College of Veterinary Medicine, Qena University, Qena, 83523, Egypt
School of International Engineering and Science, Jeonbuk National University, Jeonju, 54896, Republic of Korea

Institutions: Jeonbuk National University (South Korea)

Journal: Redox biology, volume 93, article 104155

Dates: received 11 January 2026; accepted 3 April 2026; published online 4 April 2026; in print June 2026

Type: Brief report · Language: English

License: CC BY

Identifiers: DOI 10.1016/j.redox.2026.104155 · PMID 41945998 · PMCID PMC13090729 · OpenAlex W7149660919

Open access: gold, a free copy (OpenAlex)

Status: data only

Categories: human (organism), mouse (organism), other condition (population), cellular / molecular (subfield)

Methods: Statistics

Keywords: Cell death, Ferroptosis, Neurodegenerative diseases, Pathogenesis, Prion disease, Therapeutics

MeSH: Creutzfeldt-Jakob Syndrome*, Ferroptosis*, Prion Diseases*, Amino Acid Transport System y+, Animals, Brain, Cyclohexylamines, Disease Models, Animal, Humans, Iron, Lipid Peroxidation, Mice, Neurodegenerative Diseases, Peptide Fragments, Phenylenediamines, Phospholipid Hydroperoxide Glutathione Peroxidase, Prions, Reactive Oxygen Species (* major topic)

Topic: Prion Diseases and Protein Misfolding (Molecular Biology, Biochemistry, Genetics and Molecular Biology), according to OpenAlex

Funding: National Research Foundation; NRF; Ministry of Education (2017R1A6A1A03015876, RS-2025-00517133, RS-2025-24792972, RS-2025-23963916, RS-2021-NF000550); Korea Basic Science Institute (KBSI)

Citations: cited by 2 papers (Europe PMC); 53 references in the paper

Abstract

Prion diseases are a group of fatal neurodegenerative disorders caused by misfolded proteins. Understanding the regulatory networks of ferroptosis in prion diseases could unveil new diagnostic and therapeutic strategies. To explore this, we systematically evaluated ferroptosis-associated alterations across human sporadic Creutzfeldt–Jakob disease (sCJD) brain samples, the ME7-infected mouse model, and in vitro using PrP106-126-treated SH-SY5Y cells. In sCJD patients, we observed a significant decrease in GPX4 expression, accompanied by elevated lipid peroxidation, as confirmed by malondialdehyde assays. Furthermore, in vitro experiments using PrP106-126-treated cells confirmed that ferroptosis-related mechanisms actively contribute to cell death, characterized by elevated lipid peroxidation, reactive oxygen species, and increased intracellular Fe2+ levels, as well as diminished glutathione activity. Critically, pharmacological inhibition with ferrostatin-1 effectively mitigated this neurotoxicity, consistent with a ferroptosis-related mechanism. To validate these findings in vivo, we demonstrated that ME7-infected mice exhibited significantly lower levels of GPX4 and SLC7A11, which correlated with increased 4-hydroxynonenal and neuronal damage. Finally, bioinformatic analysis of the GSE124571 dataset identified a distinct transcriptomic signature of 130 differentially expressed ferroptosis-related genes in sCJD patients. These results collectively suggest that ferroptosis-associated alterations are involved in prion-associated neurodegeneration, offering valuable pathophysiological insights into disease progression.

Reproduced under the paper's license (CC BY), from the paper cited above.

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Data

Data links

ncbi.nlm.nih.gov/geo, NCBI; found in the text, “Data acquisition and processing”

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All data are reported in the article and supplementary materials.

Reproduced under the paper's license (CC BY), from the paper cited above.

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Version 1, 28 September 2026: the first record

Recorded: type, language, journal, volume, pages, dates, 3 authors, 6 keywords, 18 MeSH terms, 4 funders, 53 references.

Cite

This paper

Zayed, M., Tayara, H., & Jeong, B.-H. (2026). Ferroptosis-related mechanisms in prion diseases provide insights into neurodegeneration and reveal therapeutic implications. Redox biology, 93, 104155. https://doi.org/10.1016/j.redox.2026.104155

BibTeX

@article{zayed2026ferroptosis, author = {Zayed, Mohammed and Tayara, Hilal and Jeong, Byung-Hoon}, title = {{Ferroptosis-related mechanisms in prion diseases provide insights into neurodegeneration and reveal therapeutic implications}}, journal = {Redox biology}, year = {2026}, month = apr, volume = {93}, pages = {104155}, publisher = {Elsevier}, issn = {2213-2317}, doi = {10.1016/j.redox.2026.104155}, url = {https://doi.org/10.1016/j.redox.2026.104155}, pmid = {41945998}, pmcid = {PMC13090729} }

RIS

TY - JOUR AU - Zayed, Mohammed AU - Tayara, Hilal AU - Jeong, Byung-Hoon TI - Ferroptosis-related mechanisms in prion diseases provide insights into neurodegeneration and reveal therapeutic implications T2 - Redox biology J2 - Redox Biol PY - 2026 DA - 2026/04/04 VL - 93 SP - 104155 SN - 2213-2317 PB - Elsevier DO - 10.1016/j.redox.2026.104155 UR - https://doi.org/10.1016/j.redox.2026.104155 LA - en ER -

CSL-JSON

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