Large-scale in vivo femtosecond laser neurosurgery screen reveals small-molecule enhancer of regeneration
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Yanik_Large-scale in vivo.pdf
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Author(s)
Gilleland, Cody Lee
Rohde, Christopher Benjamin
Samara, Chrysanthi
Yanik, Mehmet Fatih
Haggarty, Stephen J.
Date Issued
October 2010
Journal
Proceedings of the National Academy of Sciences
Publisher
National Academy of Sciences
Citation
Samara, C. et al. “Large-scale in Vivo Femtosecond Laser Neurosurgery Screen Reveals Small-molecule Enhancer of Regeneration.” Proceedings of the National Academy of Sciences 107.43 (2010): 18342–18347. © 2010 National Academy of Sciences.
Version
Final published version
Abstract
Discovery of molecular mechanisms and chemical compounds that enhance neuronal regeneration can lead to development of therapeutics to combat nervous system injuries and neurodegenerative diseases. By combining high-throughput microfluidics and femtosecond laser microsurgery, we demonstrate for the first time large-scale in vivo screens for identification of compounds that affect neurite regeneration. We performed thousands of microsurgeries at single-axon precision in the nematode Caenorhabditis elegans at a rate of 20 seconds per animal. Following surgeries, we exposed the animals to a hand-curated library of approximately one hundred small molecules and identified chemicals that significantly alter neurite regeneration. In particular, we found that the PKC kinase inhibitor staurosporine strongly modulates regeneration in a concentration- and neuronal type-specific manner. Two structurally unrelated PKC inhibitors produce similar effects. We further show that regeneration is significantly enhanced by the PKC activator prostratin.
MIT Department
Massachusetts Institute of Technology. Department of Electrical Engineering and Computer Science
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Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use.
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DOI of Published Version
https://doi.org/10.1073/pnas.1005372107
