Sci. Signal., 11 November 2008
Neuroscience Brain Repair
Pamela J. Hines
Science, AAAS, Washington, DC 20005, USA
In mammals, a severed nerve in an arm or leg will eventually regrow and reestablish functional connections. A similar injury in the spinal cord or within the brain will not be repaired, resulting in permanent disability and paralysis. Poor regeneration in the central nervous system has been attributed to proteins embedded in brain myelin (the membranes that wrap each nerve axon), which interact with an inhibitory receptor on neurons called NgR. Two papers in this issue show that other inhibitory receptors recognize the myelin-embedded proteins (see the Perspective by Kim and Snider). Atwal et al. identified PirB, a mouse protein related to the immunoglobulins of the immune system, and if both PirB and NgR were blocked, regeneration resumed. Park et al. found that after injury to the optic nerve, the axons of the retinal ganglion cells in mice will regenerate if the growth-related signaling pathway mTOR is activated in these cells. When negative regulators of the mTOR pathway were deleted in the retinas of mice, within a few weeks the axons of retinal ganglion cells would regrow as far as the optic chiasm. Thus, to promote recovery from neural damage, a combination of therapeutic approaches is needed to remove inhibitory processes, as well as to stimulate the intrinsic growth pathways of the neurons.
J. K. Atwal, J. Pinkston-Gosse, J. Syken, S. Stawicki, Y. Wu, C. Shatz, M. Tessier-Lavigne, PirB is a functional receptor for myelin inhibitors of axonal regeneration. Science 322, 967-970 (2008). [Abstract] [Full Text]
K. K. Park, K. Liu, Y. Hu, P. D. Smith, C. Wang, B. Cai, B. Xu, L. Connolly, I. Kramvis, M. Sahin, Z. He, Promoting axon regeneration in the adult CNS by modulation of the PTEN/mTOR pathway. Science 322, 963-966 (2008). [Abstract] [Full Text]
Citation: P. J. Hines, Brain Repair. Sci. Signal. 1, ec389 (2008).
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