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

• Published in: Journal of biomolecular screening Vol. 19; no. 1; pp. 44 - 56
• Main Authors: Boyd, Justin D, Lee, Peter, Feiler, Marisa S, Zauur, Nava, Liu, Min, Concannon, John, Ebata, Atsushi, Wolozin, Benjamin, Glicksman, Marcie A
• Format: Journal Article
• Language: English
• Published: United States 01.01.2014
• Subjects: Animals; Animals, Genetically Modified; Arsenites - pharmacology; Caenorhabditis elegans; Cell Line; DNA-Binding Proteins - antagonists & inhibitors; DNA-Binding Proteins - genetics; DNA-Binding Proteins - metabolism; Drug Discovery - methods; Drug Evaluation, Preclinical - methods; Gene Expression; Genes, Reporter; High-Throughput Screening Assays; Humans; Neurodegenerative Diseases - drug therapy; Neurodegenerative Diseases - genetics; Neurodegenerative Diseases - metabolism; Neuroprotective Agents - pharmacology; Recombinant Fusion Proteins - genetics; Recombinant Fusion Proteins - metabolism; Small Molecule Libraries; Sodium Compounds - pharmacology; Stress, Physiological - drug effects; high-throughput screen; protein synthesis; aggregation; amyotrophic lateral sclerosis; RNA binding protein; RNA granule

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 c...