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During autopsies of brains, of people who had lateral sclerosis (ALS, aka Lou Gehrig’s disease) or frontotemporal dementia (FTD), a protein called TDP-43 was observed to accumulate abnormally. Further studies confirmed the damaging role of TDP-43.

Aaron D. Gitler, PhD, Assistant Professor of Cell and Developmental Biology, University of Pennsylvania School of Medicine, sought a way to screen for drugs that would attack the TDP-43, but realized that they needed a way to determine its effectiveness in the shortest amount of time possible.

The researchers arrived at a novel approach of using yeast–the same cells that bakers and brewers use to make bread and beer. It turns out that TDP-43 forms clumps in yeast cells much like it does in human nerve cells, which provided the researchers a way to determine which parts cause the protein to be toxic.

TDP-43 normally remains in the nucleus of a cell, but for some unknown reason with ALS or FTD the protein moves from the nucleus to the cytoplasm of the cell. It is in the cytoplasm where TDP-43 clumps and becomes toxic. At some point the toxicity of TDP-43 overwhelms the yeast cells and prevents them from growing–creating a condition known as cell toxicity.

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