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generate synergistic effects on enhancing axon regeneration. In this regard,
combinatorial strategies to tackle multiple Cdk5-related and -unrelated
pathways may provide a promising avenue to achieve sustainable axon
regrowth and functional recovery after CNS injury. For instance,
upregulation of specific gene transcription and protein expression by
co-deletion of KLF4 and APC/Cdh1 complex may lead to sustained axon
regeneration. Moreover, concomitant inhibition of two HDACs, HDAC6,
and SIRT2, may significantly promote microtubule stabilization and axon
repair. Further characterization of Cdk5 as a regulator of axon growth will
likely present a more comprehensive picture and identify novel therapeutic
targets for promoting axon regeneration in the future. In addition, it will be
of interest to investigate how Cdk5-related pathways interplay with other
established pathways such as KLF4 transcriptional factors (
Moore et al., 2009
).
ACKNOWLEDGMENTS
We apologize to the researchers whose studies could not be discussed or cited because of
space limitation. We would like to thank Ka-Chun Lok for his help in preparing the
figure, and members of the Ip Laboratory for helpful discussion. The studies by N.Y. Ip
were supported in part by the Research Grants Council of Hong Kong (HKUST661109,
661309, 660110, 660610,660810, and 661111).
REFERENCES
Alilain, W. J., Horn, K. P., Hu, H., Dick, T. E., & Silver, J. (2011). Functional regeneration
of respiratory pathways after spinal cord injury.
Nature
,
475
, 196-200.
Atwal, J. K., Pinkston-Gosse, J., Syken, J., Stawicki, S., Wu, Y., Shatz, C., et al. (2008). PirB
is a functional receptor for myelin inhibitors of axonal regeneration.
Science
,
322
,
967-970.
Beaudette, K. N., Lew, J., & Wang, J. H. (1993). Substrate specificity characterization of a
cdc2-like protein kinase purified from bovine brain.
The Journal of Biological Chemistry
,
268
, 20825-20830.
Bloom, O. E., &Morgan, J. R. (2011). Membrane trafficking events underlying axon repair,
growth, and regeneration.
Molecular and Cellular Neurosciences
,
48
, 339-348.
Boyd, J. G., & Gordon, T. (2001). The neurotrophin receptors, trkB and p75, differentially
regulate motor axonal regeneration.
Journal of Neurobiology
,
49
, 314-325.
Bradke, F., &Dotti, C. G. (1999). The role of local actin instability in axon formation.
Science
,
283
, 1931-1934.
Bradke, F., Fawcett, J. W., & Spira, M. E. (2012). Assembly of a new growth cone after
axotomy: The precursor to axon regeneration.
Nature Reviews. Neuroscience
,
13
, 183-193.
Campbell, D. S., & Holt, C. E. (2001). Chemotropic responses of retinal growth cones
mediated by rapid local protein synthesis and degradation.
Neuron
,
32
, 1013-1026.
Cheng, Q., Sasaki, Y., Shoji, M., Sugiyama, Y., Tanaka, H., Nakayama, T., et al. (2003).
Cdk5/p35 and Rho-kinase mediate ephrin-A5-induced signaling in retinal ganglion
cells.
Molecular and Cellular Neurosciences
,
24
, 632-645.
Cheung, Z. H., Chin, W. H., Chen, Y., Ng, Y. P., & Ip, N. Y. (2007). Cdk5 is involved in
BDNF-stimulated dendritic growth in hippocampal neurons.
PLoS Biology
,
5
, e63.
