A high-content screen identifies novel compounds that inhibit stress-induced TDP-43 cellular aggregation and associated cytotoxicity.

ABSTRACT: TDP-43 is an RNA binding protein found to accumulate in the cytoplasm of brain and spinal cord from patients affected with amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD). Nuclear TDP-43 protein regulates transcription through several mechanisms, and under stressed conditions, it forms cytoplasmic aggregates that co-localize with stress granule (SG) proteins in cell culture. These granules are also found in the brain and spinal cord of patients affected with ALS and FTLD. The mechanism through which TDP-43 might contribute to neurodegenerative diseases is poorly understood. To investigate the pathophysiology of TDP-43 aggregation and to isolate potential therapeutic targets, we screened a chemical library of 75,000 compounds using high-content analysis with

SUBMITTER: Boyd JD 

PROVIDER: S-EPMC3913261 | biostudies-literature | 2014 Jan

REPOSITORIES: biostudies-literature