Excess iron buildup may weaken brain cells and raise risk of neurodegeneration, study finds
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Researchers have identified a process through which excess iron gradually weakens neurons, making them more vulnerable to stress and potentially contributing to neurodegenerative diseases such as Alzheimer's.
The findings, published in the journal Cell Death Discovery, describe a newly identified process called "chronoferroptosis", in which prolonged iron accumulation reduces the resilience of brain cells without immediately causing their death.
"Our study reveals that cells lose resilience when iron hits a certain level, making neurons more susceptible to stressors that damage or even kill them," said senior author Pam Maher of the Salk Institute for Biological Studies in the United States.
Iron is an essential mineral required for normal body function and is found in foods such as leafy green vegetables, cereals, lean meat, and seafood. Previous research has shown that iron gradually accumulates in neurons with age, but its long-term effects have remained unclear.
Using a human-derived nerve cell model, researchers compared the effects of short-term iron exposure lasting six to eight hours with chronic exposure over nine days.
They found that neurons exposed to iron for a short period showed little biochemical change and remained resilient when subjected to additional stress. In contrast, chronically exposed neurons exhibited elevated lipid peroxidation, an accumulation of harmful chemicals, depletion of protective molecules, and a marked reduction in their ability to withstand further cellular stress.
The researchers named this prolonged stress response chronoferroptosis, distinguishing it from ferroptosis, an iron-dependent form of cell death. They said the new pathway suggests that long-term iron overload can place neurons in a vulnerable state without immediately killing them.
"It's not the amount of iron that seals the fate of these cells, it's the amount of time they spend under stress," said study author Nawab John Dar.
The researchers believe iron buildup may result from a failure of neurons to export iron after it has been used, although the exact mechanism remains unclear.
They said the findings could help researchers identify the stage at which neurons begin to lose resilience, opening the possibility of developing treatments to correct iron imbalances before irreversible damage occurs.