Jeonbuk Nat'l University researchers trace brain’s fatal decay to ‘iron death’

Jeong Byung-hoon / Courtesy of Jeonbuk National University

Researchers in Korea have uncovered a key mechanism behind prion diseases, rare brain disorders caused by misfolded proteins that destroy nerve cells and are almost always fatal.

The study, led by Jeong Byung-hoon at Jeonbuk National University, found that ferroptosis — a form of iron-dependent cell death — is a key driver of nerve cell destruction in prion diseases.

Prion diseases are deadly neurodegenerative disorders caused by the buildup of misfolded proteins in the brain. They include Creutzfeldt-Jakob disease in humans and bovine spongiform encephalopathy, or mad cow disease, in animals. Despite their severity and rapid progression, no effective treatments currently exist.

The research team conducted an integrated analysis using brain tissue from patients with sporadic Creutzfeldt-Jakob disease, as well as infected mouse models and cultured human cells. The findings showed a significant decrease in the antioxidant enzyme GPX4 and an increase in lipid peroxidation markers, both hallmarks of ferroptosis.

At the cellular level, prion peptides caused cells to produce more reactive oxygen, accumulate iron, and lose glutathione, confirming that ferroptosis — a specific type of cell death — plays a key role.

The team also found that treating cells with Ferrostatin-1, a drug that blocks ferroptosis, helped neurons survive and sharply reduced oxidative stress and lipid damage. The findings suggest that prion-related nerve cell damage could be controlled by targeting ferroptosis pathways.

Similar patterns appeared in animal models. In infected mice, levels of GPX4 and SLC7A11 dropped, while oxidative stress and nerve cell damage rose, reinforcing the role of ferroptosis in disease progression. Analysis of patient samples revealed changes in 130 genes linked to ferroptosis, further supporting the findings.

The study appeared in the latest issue of the open-access journal Redox Biology and was highlighted by the Biological Research Information Center in its ‘People Who Brighten Korea’ program.

“This is a systematic study that identifies the mechanism of neuronal cell death in prion diseases from the perspective of ferroptosis,” Jeong said. “It is meaningful in that it suggests the possibility of developing treatments targeting this pathway.”

He said future drug development based on these findings could help slow disease progression and protect nerve cells.

The research was supported by the National Research Foundation of Korea through its mid-career researcher program and other initiatives, and was conducted using the research infrastructure of Jeonbuk National University’s Institute for Zoonotic Diseases and its core research support center.