Recapitulate development to promote axonal regeneration: good or bad approach? - PubMed (original) (raw)

Review

Recapitulate development to promote axonal regeneration: good or bad approach?

Marie T Filbin. Philos Trans R Soc Lond B Biol Sci. 2006.

Abstract

In the past decade there has been an explosion in our understanding, at the molecular level, of why axons in the adult, mammalian central nervous system (CNS) do not spontaneously regenerate while their younger counterparts do. Now a number of inhibitors of axonal regeneration have been described, some of the receptors they interact with to transduce the inhibitory signal are known, as are some of the steps in the signal transduction pathway that is responsible for inhibition. In addition, developmental changes in the environment and in the neurons themselves are also now better understood. This knowledge in turn reveals novel, putative sites for drug development and therapeutic intervention after injury to the brain and spinal cord. The challenge now is to determine which of these putative treatments are the most effective and if they would be better applied in combination rather than alone. In this review I will summarize what we have learnt about these molecules and how they signal. Importantly, I will also describe approaches that have been shown to block inhibitors and encourage regeneration in vivo. I will also speculate on what the differences are between the neonatal and adult CNS that allow the former to regenerate and the latter not to.

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Figures

Figure 1

Figure 1

Inhibitors of axonal regeneration, their receptors and how they signal. Three myelin inhibitors, MAG, Nogo-66 and OMgp, all interact with the NgR/Lingo/p75 (TROY) receptor complex. The receptors for Amino-Nogo and CSPGs are not known. All the inhibitors exert inhibition by activating Rho. Inactivation of Rho or elevation of cAMP each overcome all the inhibitors simultaneously. The cAMP effect is CREB- and transcription-dependent. ArgI is up-regulated, resulting in an increase in polyamine synthesis. Polyamines can block inhibition.

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