The c-Jun transcription factor – bipotential mediator of neuronal death, survival and regeneration

• Published in: Trends in neurosciences (Regular ed.) 1997-05, Vol.20 (5), p.227-231
• Main Authors: Herdegen, Thomas, Skene, Pate, Bähr, Mathias
• Format: Article
• Language: English
• Subjects: Animals; ATF-2; Axons - physiology; axotomy; Biological and medical sciences; cell body response; Cell Death - physiology; Cellular biology; Denervation; Development. Senescence. Regeneration. Transplantation; Enzyme Activation; Fundamental and applied biological sciences. Psychology; Humans; JNK; JNK Mitogen-Activated Protein Kinases; MAP Kinase Kinase 4; Medical research; Mitogen-Activated Protein Kinase Kinases; Nerve Regeneration - physiology; nervous system; Neurons; Neurons - physiology; Protein Kinases - metabolism; Proto-Oncogene Proteins c-jun - physiology; SAPK; Vertebrates: nervous system and sense organs
• ISSN: 0166-2236; 1878-108X
• DOI: 10.1016/S0166-2236(96)01000-4

Axon interruption elicits a complex neuronal response that leaves neurons poised precariously between death and regeneration. The signals underlying this dichotomy are not fully understood. The transcription factor c-Jun is one of the earliest and most consistent markers for neurons that respond to nerve-fiber transection, and its expression can be related to both degeneration and survival including target re-innervation. In vitro experiments have demonstrated that expression of c-Jun can kill neonatal neurons but, in the adult nervous system, c-Jun might also be involved in neuroprotection and regeneration. The functional characteristics of c-Jun offer a model for the ability of a single molecule to serve as pivotal regulator for death or survival, not only in the response of the cell body to axonal lesions but also following neurodegenerative disorders. In this model, the fate of neurons is determined by a novel transcriptional network comprising c-Jun, ATF-2 (activating transcription factor-2) and JNKs (c-Jun N-terminal kinases).