Inhibiting poly(ADP-ribosylation) improves axon regeneration
| Title: | Inhibiting poly(ADP-ribosylation) improves axon regeneration |
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| Authors: | Alexandra B Byrne, Rebecca D McWhirter, Yuichi Sekine, Stephen M Strittmatter, David M Miller III, Marc Hammarlund |
| Source: | eLife, Vol 5 (2016) |
| Publisher Information: | eLife Sciences Publications Ltd, 2016. |
| Publication Year: | 2016 |
| Collection: | LCC:Medicine LCC:Science LCC:Biology (General) |
| Subject Terms: | axon regeneration, poly(ADP-ribose) polymerase, poly(ADP-ribose) glycohydrolase, dlk-1/MAPKKK, Medicine, Science, Biology (General), QH301-705.5 |
| More Details: | The ability of a neuron to regenerate its axon after injury depends in part on its intrinsic regenerative potential. Here, we identify novel intrinsic regulators of axon regeneration: poly(ADP-ribose) glycohodrolases (PARGs) and poly(ADP-ribose) polymerases (PARPs). PARGs, which remove poly(ADP-ribose) from proteins, act in injured C. elegans GABA motor neurons to enhance axon regeneration. PARG expression is regulated by DLK signaling, and PARGs mediate DLK function in enhancing axon regeneration. Conversely, PARPs, which add poly(ADP-ribose) to proteins, inhibit axon regeneration of both C. elegans GABA neurons and mammalian cortical neurons. Furthermore, chemical PARP inhibitors improve axon regeneration when administered after injury. Our results indicate that regulation of poly(ADP-ribose) levels is a critical function of the DLK regeneration pathway, that poly-(ADP ribosylation) inhibits axon regeneration across species, and that chemical inhibition of PARPs can elicit axon regeneration. |
| Document Type: | article |
| File Description: | electronic resource |
| Language: | English |
| ISSN: | 2050-084X |
| Relation: | https://elifesciences.org/articles/12734; https://doaj.org/toc/2050-084X |
| DOI: | 10.7554/eLife.12734 |
| Access URL: | https://doaj.org/article/b7f2b81c9905458f8d36ba102e5a8f23 |
| Accession Number: | edsdoj.b7f2b81c9905458f8d36ba102e5a8f23 |
| Database: | Directory of Open Access Journals |
| ISSN: | 2050084X |
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| DOI: | 10.7554/eLife.12734 |
| Published in: | eLife |
| Language: | English |