The DOI matches its Crossref record; 7 of the 7 references it cites were found in a registry or an index.
A Small Molecule Screen in Stem-Cell-Derived Motor Neurons Identifies a Kinase Inhibitor as a Candidate Therapeutic for ALS
Open accessAbstract
Amyotrophic lateral sclerosis (ALS) is a rapidly progressing neurodegenerative disease, characterized by motor neuron (MN) death, for which there are no truly effective treatments. Here, we describe a new small molecule survival screen carried out using MNs from both wildtype and mutant SOD1 mouse embryonic stem cells. Among the hits we found, kenpaullone had a particularly impressive ability to prolong the healthy survival of both types of MNs that can be attributed to its dual inhibition of GSK3 and HGK kinases. Furthermore, kenpaullone also strongly improved the survival of human MNs derived from ALS patient induced pluripotent stem cells and was more active than either of two compounds, olesoxime and dexpramipexole, that recently failed in ALS clinical trials. Our studies demonstrate the value of a stem cell approach to drug discovery and point to a new paradigm for identification and preclinical testing of future ALS therapeutics.
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Cites
Ubiquitinated TDP-43 in Frontotemporal Lobar Degeneration and Amyotrophic Lateral Sclerosis
Neumann, M., Sampathu, D. M., Kwong, L. K., Truax, A. C., Micsenyi, M. C., Chou, T. T., Bruce, J., Schuck, T., Grossman, M., Clark, C. M., et al. (2006) · Science · doi:10.1126/science.1134108 · Cited by 6,576
A Hexanucleotide Repeat Expansion in C9ORF72 Is the Cause of Chromosome 9p21-Linked ALS-FTD
Renton, A. E., Majounie, E., Waite, A., Simón-Sánchez, J., Rollinson, S., Gibbs, J. R., Schymick, J. C., Laaksovirta, H., van Swieten, J. C., Myllykangas, L., et al. (2011) · Neuron · doi:10.1016/j.neuron.2011.09.010 · Cited by 4,409
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Astrocytes expressing ALS-linked mutated SOD1 release factors selectively toxic to motor neurons
Nagai, M., Re, D. B., Nagata, T., Chalazonitis, A., Jessell, T. M., Wichterle, H., & Przedborski, S. (2007) · Nature Neuroscience · doi:10.1038/nn1876 · Cited by 1,220
Non–cell autonomous toxicity in neurodegenerative disorders: ALS and beyond
Ilieva, H., Polymenidou, M., & Cleveland, D. W. (2009) · Journal of Cell Biology · doi:10.1083/jcb.200908164 · Cited by 1,008
Astrocytes from familial and sporadic ALS patients are toxic to motor neurons
Haidet-Phillips, A. M., Hester, M. E., Miranda, C. J., Meyer, K., Braun, L., Frakes, A., Song, S., Likhite, S., Murtha, M. J., Foust, K. D., et al. (2011) · Nature Biotechnology · doi:10.1038/nbt.1957 · Cited by 782
Antisense oligonucleotide therapy for neurodegenerative disease
Smith, R. A. (2006) · Journal of Clinical Investigation · doi:10.1172/jci25424 · Cited by 506
Cited by
C9orf72-mediated ALS and FTD: multiple pathways to disease
Balendra, R., & Isaacs, A. M. (2018) · Nature Reviews Neurology · doi:10.1038/s41582-018-0047-2 · Cited by 715
Xu, M., Lee, E. M., Wen, Z., Cheng, Y., Huang, W.-K., Qian, X., TCW, J., Kouznetsova, J., Ogden, S. C., Hammack, C., et al. (2016) · Nature Medicine · doi:10.1038/nm.4184 · Cited by 641
Pluripotent stem cells in disease modelling and drug discovery
Avior, Y., Sagi, I., & Benvenisty, N. (2016) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm.2015.27 · Cited by 592
Czerniecki, S. M., Cruz, N. M., Harder, J. L., Menon, R., Annis, J., Otto, E. A., Gulieva, R. E., Islas, L. V., Kim, Y. K., Tran, L. M., et al. (2018) · Cell Stem Cell · doi:10.1016/j.stem.2018.04.022 · Cited by 465
Emde, A., Eitan, C., Liou, L., Libby, R. T., Rivkin, N., Magen, I., Reichenstein, I., Oppenheim, H., Eilam, R., Silvestroni, A., et al. (2015) · The EMBO Journal · doi:10.15252/embj.201490493 · Cited by 217
Metadata
- Authors
- Yang, Y. M., Gupta, S. K., Kim, K. J., Powers, B. E., Cerqueira, A., Wainger, B. J., Ngo, H. D., Rosowski, K. A., Schein, P. A., Ackeifi, C. A., Arvanites, A. C., Davidow, L. S., Woolf, C. J., & Rubin, L. L.
- Venue
- Cell Stem Cell
- Publisher
- Elsevier BV
- Published
- 2013-06
- Volume
- 12
- Issue
- 6
- Pages
- 713-726
- ISSN
- 1875-9777 (ISSN-L)
- 1934-5909
- OpenAlex
- W2009108898
- Cited by
- 305
- References
- 7
- FWCI
- 26.60
- Type
- journal article
- Language
- en
- Open access
- bronze
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- Yang, Y. M., Gupta, S. K., Kim, K. J., Powers, B. E., Cerqueira, A., Wainger, B. J., Ngo, H. D., Rosowski, K. A., Schein, P. A., Ackeifi, C. A., Arvanites, A. C., Davidow, L. S., Woolf, C. J., & Rubin, L. L. (2013). A Small Molecule Screen in Stem-Cell-Derived Motor Neurons Identifies a Kinase Inhibitor as a Candidate Therapeutic for ALS. Cell Stem Cell. https://doi.org/10.1016/j.stem.2013.04.003
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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