FunGen-AD research identifies vitamin that could protect against manganese-induced brain damage

Manganese is an essential mineral that is part of a healthy diet, but chronic, long-term exposure to manganese through jobs like welding and mining or drinking contaminated water can lead to motor symptoms like muscle stiffness and tremors with Parkinson’s disease (PD), also known as parkinsonism. Researchers, including FunGen-AD investigators Gary Miller and Yunjia Lai at Columbia University, developed a parkinsonism model to study the molecular mechanisms through which manganese damages the central nervous system. This model led to identification of a potential preventive treatment for manganese-induced parkinsonism.

The researchers developed a Drosophila model of manganese toxicity and characterized the effects on brain structure and motor function. These fruit flies had a reduced lifespan and showed motor deficits, neuronal loss, decreased dopamine levels, and mitochondrial and lysosomal dysfunction. These findings were validated in human dopaminergic neurons derived from induced pluripotent stem cells (iPSCs). A metabolomics analysis of the brains from Drosophila exposed to manganese showed significant increases in biotin, which is a B vitamin. Further analyses showed that biotin enhanced dopamine production in the brain, and supplementation with biotin improved mitochondrial function and reduced neuronal loss in Drosophila and iPSC-derived neurons exposed to manganese. These results indicate that biotin is a preventive therapy for parkinsonism caused by manganese exposure. Biotin has already been shown to be safe and well-tolerated by humans, making it a promising treatment option worthy of further exploration.

This research, partially supported by FunGen-AD grants R01AG067501 and RF1AG066107, is published in Science Signaling here. You can read more about these research findings at the following links: