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

Journal of Biomolecular Screening

Volumn 19, Issue 1, 2014, Pages 44-56

  Boyd, Justin D ^a   Peter Lee Armandt, J ^b   Feiler, Marisa S ^b   Zaarur, Nava ^b   Liu, Min ^a   Kraemer, Brian ^c   Concannon, John B ^a   Ebata, Atsushi ^b,d   Wolozin, Benjamin ^b,d   Glicksman, Marcie A ^a  

^a BRIGHAM AND WOMEN S HOSPITAL   (United States)

^b BOSTON UNIVERSITY   (United States)

^c VA PUGET SOUND HEALTH CARE SYSTEM   (United States)

^d BOSTON UNIVERSITY SCHOOL OF MEDICINE   (United States)

Author keywords

aggregation; amyotrophic lateral sclerosis; high throughput screen; protein synthesis; RNA binding protein; RNA granule

Indexed keywords

GREEN FLUORESCENT PROTEIN; TAR DNA BINDING PROTEIN;

ANIMAL CELL; ARTICLE; CAENORHABDITIS ELEGANS; CELL AGGREGATION; CONTROLLED STUDY; CYTOTOXICITY; INHIBITION KINETICS; MOLECULAR LIBRARY; NONHUMAN; PC12 CELL; PHENOTYPE; PRIORITY JOURNAL; PROTEIN ANALYSIS; PROTEIN EXPRESSION; RAT; REGULATORY MECHANISM; STRESS; WESTERN BLOTTING;

AGGREGATION; AMYOTROPHIC LATERAL SCLEROSIS; HIGH-THROUGHPUT SCREEN; PROTEIN SYNTHESIS; RNA BINDING PROTEIN; RNA GRANULE;

ANIMALS; ANIMALS, GENETICALLY MODIFIED; ARSENITES; CAENORHABDITIS ELEGANS; CELL LINE; DNA-BINDING PROTEINS; DRUG DISCOVERY; DRUG EVALUATION, PRECLINICAL; GENE EXPRESSION; GENES, REPORTER; HIGH-THROUGHPUT SCREENING ASSAYS; HUMANS; NEURODEGENERATIVE DISEASES; NEUROPROTECTIVE AGENTS; RECOMBINANT FUSION PROTEINS; SMALL MOLECULE LIBRARIES; SODIUM COMPOUNDS; STRESS, PHYSIOLOGICAL;

EID: 84890817663     PISSN: 10870571     EISSN: 1552454X     Source Type: Journal    
DOI: 10.1177/1087057113501553     Document Type: Article

References (28)

1. Mitchell J. D., Borasio G. D.. Amyotrophic Lateral Sclerosis. Lancet. 2007 ; 369: 2031-2041
2. Lambrechts D., Storkebaum E., Carmeliet P.. VEGF: Necessary to Prevent Motoneuron Degeneration, Sufficient to Treat ALS?. Trends Mol. Med. 2004 ; 10: 275-282
3. Neumann M., Sampathu D. M., Kwong L. K., et al. Ubiquitinated TDP-43 in Frontotemporal Lobar Degeneration and Amyotrophic Lateral Sclerosis. Science. 2006 ; 314: 130-133
4. Sreedharan J., Blair I. P., Tripathi V. B., et al. TDP-43 Mutations in Familial and Sporadic Amyotrophic Lateral Sclerosis. Science. 2008 ; 319: 1668-1672
5. Gitcho M. A., Baloh R. H., Chakraverty S., et al. TDP-43 A315T Mutation in Familial Motor Neuron Disease. Ann. Neurol. 2008 ; 63: 535-538
6. Lee E. B., Lee V. M., Trojanowski J. Q.. Gains or Losses: Molecular Mechanisms of TDP43-Mediated Neurodegeneration. Nat. Rev. Neurosci. 2011 ; 13: 38-50
7. Barmada S. J., Skibinski G., Korb E., et al. Cytoplasmic Mislocalization of TDP-43 Is Toxic to Neurons and Enhanced by a Mutation Associated with Familial Amyotrophic Lateral Sclerosis. J. Neurosci. 2010 ; 30: 639-649
8. Liu-Yesucevitz L., Bilgutay A., Zhang Y., et al. Tar DNA Binding Protein-43 (TDP-43) Associates with Stress Granules: Analysis of Cultured Cells and Pathological Brain Tissue. PLoS One. 2010 ; 5: e13250
9. Wolozin B.. Regulated Protein Aggregation: Stress Granules and Neurodegeneration. Mol. Neurodegener. 2012 ; 7: 56
10. Anderson P., Kedersha N.. Stress Granules: the Tao of RNA Triage. Trends Biochem. Sci. 2008 ; 33: 141-150
11. Kedersha N., Anderson P.. Stress Granules: Sites of mRNA Triage That Regulate mRNA Stability and Translatability. Biochem. Soc. Trans. 2002 ; 30: 963-969
12. Lagier-Tourenne C., Polymenidou M., Cleveland D. W.. TDP-43 and FUS/TLS: Emerging Roles in RNA Processing and Neurodegeneration. Hum. Mol. Genet. 2010 ; 19: R46 - R64
13. Thomas M. G., Loschi M., Desbats M. A., et al. RNA Granules: The Good, the Bad and the Ugly. Cell Signal. 2011 ; 23: 324-334
14. Colombrita C., Zennaro E., Fallini C., et al. TDP-43 Is Recruited to Stress Granules in Conditions of Oxidative Insult. J. Neurochem. 2009 ; 111: 1051-1061
15. Winton M. J., Igaz L. M., Wong M. M., et al. Disturbance of Nuclear and Cytoplasmic TAR DNA-Binding Protein (TDP-43) Induces Disease-Like Redistribution, Sequestration, and Aggregate Formation. J. Biol. Chem. 2008 ; 283: 13302-13309
16. Brenner S.. The Genetics of Caenorhabditis elegans. Genetics. 1974 ; 77: 71-94
17. Liachko N. F., Guthrie C. R., Kraemer B. C.. Phosphorylation Promotes Neurotoxicity in a Caenorhabditis elegans Model of TDP-43 Proteinopathy. J Neurosci. 2010 ; 30: 16208-16219
18. Jain S., Heutink P.. From Single Genes to Gene Networks: High-Throughput-High-Content Screening for Neurological Disease. Neuron. 2011 ; 68: 207-217
19. Iguchi Y., Katsuno M., Takagi S., et al. Oxidative Stress Induced by Glutathione Depletion Reproduces Pathological Modifications of TDP-43 Linked to TDP-43 Proteinopathies. Neurobiol. Dis. 2012 ; 45: 862-870
20. Liachko N. F., McMillan P. J., Guthrie C. R., et al. CDC7 Inhibition Blocks Pathological TDP-43 Phosphorylation and Neurodegeneration. Ann. Neurol.. :
21. Meyerowitz J., Parker S. J., Vella L. J., et al. C-Jun N-terminal Kinase Controls TDP-43 Accumulation in Stress Granules Induced by Oxidative Stress. Mol. Neurodegener. 2011 ; 6: 57
22. Suzuki H., Matsuoka M.. The JNK/c-Jun Signaling Axis Contributes to the TDP-43-Induced Cell Death. Mol. Cell Biochem. 2013 ; 372: 241-248
23. Parker S. J., Meyerowitz J., James J. L., et al. Inhibition of TDP-43 Accumulation by Bis(thiosemicarbazonato)-Copper Complexes. PLoS One. 2012 ; 7: e42277
24. Cassel J. A., Reitz A. B.. Ubiquilin-2 (UBQLN2) Binds with High Affinity to the C-terminal Region of TDP-43 and Modulates TDP-43 Levels in H4 Cells: Characterization of Inhibition by Nucleic Acids and 4-Aminoquinolines. Biochim. Biophys. Acta. 2013 ; 1834: 964-971
25. Wang I. F., Chang H. Y., Hou S. C., et al. The Self-Interaction of Native TDP-43 C Terminus Inhibits Its Degradation and Contributes to Early Proteinopathies. Nat. Commun. 2012 ; 3: 766
26. Jinwal U. K., Abisambra J. F., Zhang J., et al. Cdc37/Hsp90 Protein Complex Disruption Triggers an Autophagic Clearance Cascade for TDP-43 Protein. J. Biol. Chem. 2012 ; 287: 24814-24820
27. Egawa N., Kitaoka S., Tsukita K., et al. Drug Screening for ALS Using Patient-Specific Induced Pluripotent Stem Cells. Sci. Transl. Med. 2012 ; 4 :
28. Dragunow M.. The Adult Human Brain in Preclinical Drug Development. Nat. Rev. Drug Discov. 2008 ; 7: 659-666