Abstract
In the adult mammalian central nervous system (CNS), the axons do not spontaneously
regenerate after injury due to the inhibitory extrinsic environment and a diminished
intrinsic regenerative capability. Many previous studies focus largely on characterizing
the hostile growth inhibitory molecules in the CNS. In fact, blocking such inhibitory
activities by either genetic or pharmacological approaches only allows limited sprouting,
and majority of the adult neurons fail to regenerate their axons even provided with
permissive substrates. Upon the neural circuits established during development, the
intrinsic neuronal growth activity is gradually repressed. Little is known to the
mechanisms for transition from the robust growth mode of the immature neurons to the
poor growth mode of the mature neurons and the way to reactivate the intrinsic growth
capacity after injury. The primary sensory neurons with cell bodies in the dorsal
root ganglion (DRG) provide a useful model to develop strategies to enhance the intrinsic
growth capacity of neurons. The centrally projecting axons in the adult spinal cord
do not regenerate, while the peripheral branches regenerate robustly after injury.
Regeneration of the central branches can be significantly enhanced after a prior peripheral
branch injury, which is defined as conditioning lesion. We reviewed the mode of conditioning
lesion reactivating the intrinsic growth program. Importantly, we summarized the intrinsic
neuronal determinants for neurite growth such as cAMP, PTEN/mTOR, APC-Cdh1, KLF4,
etc., the mechanisms underlying development-dependent decline of CNS neurons growth
ability, and procedures to enhance the intrinsic growth potential.
Keywords
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Article info
Publication history
Published online: September 19, 2011
Accepted:
August 26,
2011
Received in revised form:
August 23,
2011
Received:
June 23,
2011
Identification
Copyright
© 2011 Elsevier B.V. Published by Elsevier Inc. All rights reserved.
