November 26, 2014

New tools to probe manganese biology

Vanderbilt researchers have developed tools to probe the role of the essential metal manganese in neurons, and which offer a started point for developing therapeutic agents for manganese-related neurological disorders.

The essential metal manganese is a required cofactor for a variety of enzymes, but in excess, it is neurotoxic and has been implicated in neurodegenerative disorders including Parkinson’s and Huntington’s disease.

Little is known about the intracellular processes that regulate manganese balance. To develop tools for probing manganese biology, Aaron Bowman, Ph.D., Kevin Kumar, an MSTP graduate student, and colleagues performed a high throughput screen for small molecules that modify manganese content in neurons.

The work culminated in a “chemical toolbox” that they used to study manganese handling by the human neurons that degenerate in Parkinson’s disease. They discovered that the small molecules had different effects on manganese content depending on the developmental stage of the neurons.

The small molecules, described in Scientific Reports, provide a valuable resource for studying manganese biology and offer a starting point for developing therapeutic agents for neurological disorders associated with disruption of manganese biology.

This research was supported by grants from the National Institutes of Health (ES000267, ES016931, ES010563, GM080403, MH090192, GM099842, DK097376).

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