Neuronal Signalling Pathways Controlling Axon Growth and Regeneration

Andrew John Murray, Derryck Shewan

Research output: Contribution to conferencePoster

Abstract

The search for an effective therapy for repairing the damaged central nervous system (CNS) remains one of the greatest challenges facing medical science. Damage to the brain or spinal cord is so debilitating because the adult mammalian CNS does not regenerate after injury. However, the immature nervous system can regenerate, and thus the ability of neurons to regrow their axonal processes is only lost around birth. A number of reasons have been proposed for this developmental decline in regenerative capacity. Cyclic-adenosine monophosphate (cAMP) is an important intracellular signalling molecule known to be involved in neuronal responses to a number of axon growth-promoting and inhibitory guidance cues. Endogenous levels of cAMP decline at the time the nervous system loses its regenerative capacity. Artificial elevation of cAMP activity can overcome growth-inhibitory signals and enhance axon outgrowth. Thus an increase in cAMP activity appears to encourage older neurons to behave like their younger counterparts in regenerating axons.

However, the signalling mechanisms activated by cAMP to induce axon regeneration are not well understood. cAMP is known to have two direct intracellular targets, protein kinase A (PKA) and the recently characterised exchange protein activated by cAMP (Epac). Previous studies have indicated that PKA controls cAMP’s growth promoting ability. However, using selective cAMP agonists and siRNA techniques we have found that cAMP’s activation of Epac is critical to increase axon growth and regeneration, and direct Epac activation can be more effective at inducing regeneration than cAMP elevation. Furthermore, we have found that Epac and PKA mediate distinct aspects of axon growth. These results provide further characterisation of the neuronal signalling pathways that can be targeted to induce axon regeneration and provide further optimism for a future therapeutic strategy.
Original languageEnglish
Publication statusPublished - 31 Aug 2007
EventScottish Neuroscience Group Annual Meeting (2007) - Edinburgh, United Kingdom
Duration: 31 Aug 2007 → …

Conference

ConferenceScottish Neuroscience Group Annual Meeting (2007)
CountryUnited Kingdom
CityEdinburgh
Period31/08/07 → …

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    Murray, A. J., & Shewan, D. (2007). Neuronal Signalling Pathways Controlling Axon Growth and Regeneration. Poster session presented at Scottish Neuroscience Group Annual Meeting (2007), Edinburgh, United Kingdom.