Abstract:

cAMP signaling in neurons and Schwann cells: a common second messenger underlies promotion of axon regeneration and the onset of myelination. The ubiquitous second messenger cyclic adenosine monophosphate (cAMP) is the central player of one of the most complex signaling systems that operate in eukaryotic cells. cAMP is able to control a variety of cellular responses in a cell type-specific and stimulus-dependent manner through an elaborate network of signaling intermediaries and effectors that connect stimulation of receptors in the cell membrane to activation of transcription factors in the nucleus. It has been well-recognized that cAMP signaling regulates multiple aspects of the life of neurons and Schwann cells (SCs), including their survival, lineage specification and differentiation. In CNS and PNS neurons, cAMP promotes growth and guidance of axons by acting both at the level of the growth cone and the nucleus to drive transcriptional programs that sustain axonal outgrowth. In mature central neurons, cAMP elevation supports axon regeneration by allowing neurons to overcome the inhibitory effect of signals present in CNS myelin and the glial scar.