TDP-43 has been recognized as the main component of ubiquitin-positive protein inclusions in ALS cases. Several recent studies demonstrate that TDP-43 truncation and aggregation are involved in TDP-43 neurotoxicity, and may play a role in ALS pathogenesis. TDP-43 aggregation is accompanied by its translocation into the cytosol, depleting it from the nucleus where it plays role in transcript regulation. The goal of this project is to identify key RNA targets regulated by TDP-43 that may be aberrantly altered in ALS. These studies will provide valuable insight regarding TDP-43 function and the mechanisms by which TDP-43 loss of function may contribute to neurodegeneration. Since the majority of ALS cases show TDP-43-associated pathology, the identification of RNA targets of TDP-43 misregulated in ALS tissue will likely lead to a better understanding of mechanisms that lead to neurodegeneration in ALS patients.
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- ALS Association