Axon regeneration in the mature central nervous system is limited by extrinsic 
inhibitory signals and a postnatal decline in neurons' intrinsic growth 
capacity. Neuronal levels of the second messenger cAMP are important in 
regulating both intrinsic growth capacity and neurons' responses to extrinsic 
factors. Approaches which increase intracellular cAMP in neurons enhance neurite 
outgrowth and facilitate regeneration after injury. Thus, understanding the 
factors which affect cAMP in neurons is of potential therapeutic importance. 
Recently, soluble adenylyl cyclase (sAC, ADCY10), the ubiquitous, 
non-transmembrane adenylyl cyclase, was found to play a key role in neuronal 
survival and axon growth. sAC is activated by bicarbonate and cations and may 
translate physiologic signals from metabolism and electrical activity into a 
neuron's decision to survive or regenerate. Here we critically review the 
literature surrounding sAC and cAMP signaling in neurons to further elucidate 
the potential role of sAC signaling in neurite outgrowth and regeneration. This 
article is part of a Special Issue entitled: The role of soluble adenylyl 
cyclase in health and disease.