| First Author | Simon DJ | Year | 2012 |
| Journal | J Neurosci | Volume | 32 |
| Issue | 49 | Pages | 17540-53 |
| PubMed ID | 23223278 | Mgi Jnum | J:193196 |
| Mgi Id | MGI:5467887 | Doi | 10.1523/JNEUROSCI.3012-12.2012 |
| Citation | Simon DJ, et al. (2012) A caspase cascade regulating developmental axon degeneration. J Neurosci 32(49):17540-53 |
| abstractText | Axon degeneration initiated by trophic factor withdrawal shares many features with programmed cell death, but many prior studies discounted a role for caspases in this process, particularly Caspase-3. Recently, Caspase-6 was implicated based on pharmacological and knockdown evidence, and we report here that genetic deletion of Caspase-6 indeed provides partial protection from degeneration. However, we find at a biochemical level that Caspase-6 is activated effectively only by Caspase-3 but not other "upstream" caspases, prompting us to revisit the role of Caspase-3. In vitro, we show that genetic deletion of Caspase-3 is fully protective against sensory axon degeneration initiated by trophic factor withdrawal, but not injury-induced Wallerian degeneration, and we define a biochemical cascade from prosurvival Bcl2 family regulators to Caspase-9, then Caspase-3, and then Caspase-6. Only low levels of active Caspase-3 appear to be required, helping explain why its critical role has been obscured in prior studies. In vivo, Caspase-3 and Caspase-6-knockout mice show a delay in developmental pruning of retinocollicular axons, thereby implicating both Caspase-3 and Caspase-6 in axon degeneration that occurs as a part of normal development. |
