RESEARCH PROFILES

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L1 and its role in the recovery
of damaged nervous system functions

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By Melitta Schachner, Zentrum für Molekulare Neurobiologie
University of Hamburg, Germany

When the adult brain and spinal cord (parts of the central nervous system) are damaged, regeneration of nervous system functions is limited. Factors which can prevent regeneration include: (i) glial scars which form barriers for regrowing connections among nerve cells, (ii) a low abundance of factors that help nerve cells to survive and regrow, (iii) the presence of molecules inhibiting regrowth of damaged nerve cells, and (iv) a low abundance of molecules which promote regrowth of nerve cells. This latter explanation is consistent with the observation that L1 (a growth and nerve cell survival-promoting neural adhesion molecule) is not expressed by the glial cells of the damaged central nervous system (glial cells provide support, protection and nourishment to cells in the brain). The important question is whether L1 could help rejuvenate the damaged central nervous system of adult humans. During human embryonic development, L1 is an important molecule because it has shown to be beneficial in the formation of connections among nerve cells that are crucial for the coordinated functioning of the nervous system.

Studies by a research team lead by Melitta Schachner at University of Hamburg in Germany found that L1 can overcome many of the inhibitory cues that prevent nerve cell regrowth in the adult central nervous system of mammals. Application of L1 to adult rats after spinal cord injury promoted locomotor recovery. In addition, L1 expressed by juvenile cells in the nervous system (stem cells) increased their migratory capacity and survival and rescued dysfunctional neurons much more efficiently than L1 negative stem cells. L1 also acts as a navigator for cells that are crucial for making appropriate connections among nerve cells - a prerequisite for the proper function of the brain and spinal cord. Furthermore, they have found that L1 enhances maturation stem cells into nerve cells and that L1 expressing embryonic stem cells exhibit enhanced survival and reduced tumor formation in comparison to L1 negative cells in the damaged spinal cord of adult mice.

Thus a simple molecule such as L1 is an important player in cell interactions not only during development of the embryo, but also in the adult nervous system that is under constraint to regenerate. The manufacturing of small compounds derived from the structure of L1 should be helpful in deriving therapeutically active molecules that would promote functional recovery in spinal cord injured individuals. These compounds are likely to best display their potential for regeneration in the context of a combined therapy, where neutralization of inhibitory cues of the central nervous system together with the enhancement of the conducive mechanisms as exemplified by L1 would form the basis for a drug design in the treatment of a spinal cord injury. The CSRO is committed to continuing to fund Dr. Schachner studies on L1 and will keep you updated on her team’s results.