Award
NIH Reporter #1K22AG086336-01
Identifying and characterizing new therapy targets in TDP-43 proteinopathies
Recipient
Washington University, Saint Louis, MO
Award Amount
$162,000.00
Ceiling
$162,000.00
Awarded
February 27, 2026
Identifier
1K22AG086336-01
This award funds research to identify and characterize new therapeutic targets in TDP-43 proteinopathies, focusing on the role of ATXN3 and MARK3 in neurodegenerative diseases such as ALS, FTD, and Alzheimer's disease.
Description
The project aims to determine the functional significance of ATXN3 alternative polyadenylation and identify cellular pathways to modulate ATXN3 expression in human neurons. It also explores the regulation of TDP-43, a key RNA-binding protein, and its impact on RNA metabolism, splicing, and polyadenylation, focusing on the gene MARK3, a tau kinase associated with early tau phosphorylation in Alzheimer's disease. The research objectives include studying ATXN3 as a modifier of TDP-43 pathology, exploring post-transcriptional regulation of MARK3 as a mechanistic link between TDP-43 and tau pathology, and developing cellular tools to investigate TDP-43 mislocalization mechanisms.