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GEN News Highlights : Apr 18, 2008

Scientists Develop Yeast-Based Genetic Screen for Protein Linked to ALS and FTD

Tool can be used to identify proteins that reverse the harmful effects of TDP-43, as described in PNAS.

Researchers from the University of Pennsylvania School of Medicine have developed a yeast model that can screen for proteins that combat certain neurodegenerative diseases.

Past research has found a number of mutations in a disease protein called TDP-43, which is implicated in amyotrophic lateral sclerosis (ALS) and certain types of frontotemporal dementia (FTD), the scientists comment.

Based on these studies suggesting TDP-43 as a cause of ALS and FTD, the Penn team created a yeast model to express this protein. They found that TDP-43 formed clumps in the yeast model in the same way that it does in human nerve cells. They also identified particular segments of the mutated TDP-43 protein that cause it to aggregate and which parts cause it to be toxic.

The scientists were able to replicate the clumping process of proteins, which takes decades in humans, within hours in yeast cells. This allows for visualization of the clumping, rapid genetic screening to identify proteins that can reverse the harmful effects of the disease protein, and testing molecules that could eliminate or prevent clumping.

The Penn team is now pursuing drug screens with their TDP-43 model. The current study also involved scientists from Johns Hopkins and the Whitehead Institute for Biomedical Research. Findings are published in this weeks advance online issue of the Proceedings of the National Academy of Sciences.