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Neuronal determinants for
axon growth capacity
Injury signal
￿ Rapid responses to axotomy-
calcium influx and changes in
electrical activity
￿ Induction RAG expression
￿ Enhancement in protein synthesis
￿ Microtubule reorganization and assembly
￿ Blockage of retrograde transport of
target derived neurotrophic factors
For example, mTOR, STAT3, NFAT, CREB,
c-Jun, ATF3, SOX11, KLF family
members, and cAMP
￿ Retrograde transport of injury
signal (e.g., STAT3, ERK, and JIP)
￿ Injury-induced production
cytokines around the lesion site and
soma (e.g., LIF, CNTF, and IL-6)
Re-growing axon
Axotomy
Figure 7.3 A model for axon regeneration after injury. Upon axonal injury, several
immediate changes convey signals to initiate axon regrowth. These early signal include
abrupt elevation of intracellular Ca and interruption of electrical activity. Anterograde
and retrograde trafficking of vesicles and trophic factors are also interrupted. Injury-
induced cytokines are upregulated at the injury site and around the neuronal cell body,
which likely operate as injury-induced signals for triggering axon growth program. For
successful regeneration, injury signals (e.g., Importing, STAT3, and ERK) are conveyed
retrogradely to the cell body. Importantly, an injured neuron must be capable of sensing
these signals and also have sufficient cellular machineries to facilitate transcription of
regeneration-associated genes (RAG), enhanced protein synthesis and cytoskeletal
reorganization.
pathways and their downstream effectors during the regenerative response
will be a major challenge for future research. Second, what is the
functional outcome of new connections resulting from PTEN and
SOCS3 manipulation? Sustained and long-distance axon regeneration is
likely to be crucial for meaningful functional recovery after many forms
of CNS injury including spinal cord injury and optic neuropathy. In
addition to axon elongation, however, regenerated axons must find their
appropriate targets and make productive functional connections. Given
that perturbing PTEN and SOCS3 pathways in neurons alter normal
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