| First Author | Kaplan A | Year | 2017 |
| Journal | Neuron | Volume | 93 |
| Issue | 5 | Pages | 1082-1093.e5 |
| PubMed ID | 28279353 | Mgi Jnum | J:256126 |
| Mgi Id | MGI:6114215 | Doi | 10.1016/j.neuron.2017.02.018 |
| Citation | Kaplan A, et al. (2017) Small-Molecule Stabilization of 14-3-3 Protein-Protein Interactions Stimulates Axon Regeneration. Neuron 93(5):1082-1093.e5 |
| abstractText | Damaged central nervous system (CNS) neurons have a poor ability to spontaneously regenerate, causing persistent functional deficits after injury. Therapies that stimulate axon growth are needed to repair CNS damage. 14-3-3 adaptors are hub proteins that are attractive targets to manipulate cell signaling. We identify a positive role for 14-3-3s in axon growth and uncover a developmental regulation of the phosphorylation and function of 14-3-3s. We show that fusicoccin-A (FC-A), a small-molecule stabilizer of 14-3-3 protein-protein interactions, stimulates axon growth in vitro and regeneration in vivo. We show that FC-A stabilizes a complex between 14-3-3 and the stress response regulator GCN1, inducing GCN1 turnover and neurite outgrowth. These findings show that 14-3-3 adaptor protein complexes are druggable targets and identify a new class of small molecules that may be further optimized for the repair of CNS damage. |
