Two Proteins May Be Useful In Initiating Nerve Regeneration In Spinal Cord Injuries

Adult neurons in the central nervous system cannot regrow damaged axons, which is why patients often do not recover from spinal cord injury. In this issue (Nature Neuroscience, Vol. 4, Issue 1, 01 Jan 2001), Pate Skene and colleagues identify two proteins that together are sufficient to reactivate the growth potential of adult spinal cord axons. Previous research has defined two obstacles to regeneration of adult central neurons: an inhibitory environment for axon growth, and loss of the intrinsic axon growth capacity found in young neurons. Intrinsic growth capacity was defined in previous studies on dorsal root ganglion neurons, which have both a central axon projecting up the spinal cord and an additional axon branch that projects through a peripheral nerve. As expected, the peripheral axon can regrow after damage. However, damage to the peripheral axon also induces a program of gene expression that allows the spinal cord axon to grow over long distances within a permissive growth environment (such as a peripheral nerve graft). Skene and colleagues set out to determine what genes are turned on to allow this regrowth. Using transgenic mice, they determined that two growth-associated proteins, CAP-23 and GAP-43, which are normally found at the growing tip of embryonic axons, when expressed together in adult dorsal root ganglion neurons are sufficient to activate this intrinsic growth activity without the need for a peripheral injury. This raises the possibility that these proteins may be useful in initiating nerve regeneration in patients with spinal cord injuries, perhaps in combination with therapies to neutralize the inhibitory environment of the adult central nervous system.

Clifford Woolf discusses this work in an accompanying News & Views article.

Contacts:

Dr. J.H. Pate Skene
Department of Neurobiology
Duke University Medical Center
Durham, North Carolina 27710
USA
tel: +1 919 681 6346
fax: +1 919 684 4431
e-mail: skene@neuro.duke.edu

Dr. Clifford J. Woolf
Massachusetts General Hosp. & Harvard Med School
149 13th Street, Room 4309
Charlestown, Massachusetts 02129
USA
tel: +1 617 724 3622
fax: +1 617 724 3632
e-mail: woolf.clifford@mgh.harvard.edu

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