Cornell researchers have identified a key mechanism the brain uses to protect itself from dangerous manganese buildup, a discovery that could have implications for workers exposed to industrial metals and communities with elevated manganese levels in drinking water.
The study, published in April in The Journal of Nutrition, found that a protein known as ZIP14 plays a critical role in removing excess manganese from the brain before it can cause neurological damage.
Manganese is an essential nutrient in small amounts, helping the body regulate enzymes and brain function. But excessive exposure has long been linked to serious neurological problems, including tremors, muscle stiffness, cognitive decline and symptoms resembling Parkinson’s disease.
Researchers said the findings may be particularly relevant for welders, miners and people living near industrial sites where airborne manganese exposure can occur.
The study also raises broader public health questions because manganese can be present in drinking water and infant formula.
“The brain has ways to protect itself from toxic buildup, but we haven’t fully understood how that works,” said Tolunay Beker Aydemir, assistant professor of molecular nutrition at Cornell and senior author of the study.
The research focused on the blood-brain barrier, the highly selective network of cells that regulates what enters and exits the brain.
Cornell researchers discovered that the ZIP14 protein shifts position inside those cells when manganese levels rise, concentrating on the side facing the brain to help move excess metal back into the bloodstream for removal.
Researchers compared the process to moving additional pumps into place during a flood.
To study the mechanism, the Cornell team used advanced expansion microscopy technology capable of enlarging microscopic brain structures for detailed imaging.
The researchers also engineered mice lacking the ZIP14 protein in brain blood vessel cells. Those mice accumulated significantly higher manganese levels in their brains after exposure to the metal.
Importantly, researchers found ZIP14 did not appear responsible for stopping manganese from entering the brain initially. Instead, its primary role was helping the brain clear the metal once levels became too high.
Mice lacking the protein also showed impaired recognition memory, though researchers noted motor skills appeared largely unaffected.
The findings may help scientists better understand both rare genetic disorders tied to manganese poisoning and broader environmental exposure risks.
Researchers said the study also suggests ZIP14 could help regulate other potentially harmful metals, including iron, zinc and cadmium.
As concerns grow over industrial contamination and environmental exposure to heavy metals, the study offers new insight into how the brain naturally defends itself — and what happens when those defenses fail.
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