Role of MAG as an Axon Growth Inhibitory Protein for Regeneration of Injured Neurons in the CNS

Abstract

Following trauma in the adult central nervous system (CNS) of mammals, injured neurons do not regenerate their transected axons. An important barrier to regeneration is an axon growth inhibitory activity that is present in CNS myelin (Schwab et al, 1993). The growth inhibitory properties of CNS myelin have been demonstrated by a wide variety of techniques in a number of different laboratories, yet until recently the identity of specific proteins important for the inhibitory activity remained elusive. It is now clear that multiple proteins in myelin have growth inhibitory activity (Caroni and Schwab. 1988a; 1988b; McKerracher et al, 1994) and the search for the identity of the myelin-derived growth inhibitory proteins continues to be an important domain of research in this field. One growth inhibitory protein that has been identified recently is a known component of myelin, the myelin-associated glycoprotein (MAG) (McKerracher et al, 1994: Mukhopadhav et al, 1994). The discovery of MAG as an inhibitor of neurite outgrowth was surprising because, previously, the homology of MAG with other members of the immunoglobulin family of adhesion molecules suggested an adhesive function (Arquint et al, 1987; Salzer et al, 1987). Indeed, for certain embryonic neurons it can promote adhesion (Sadoul et al. 1990; Johnson et al, 1989; Mukhopadhay et al 1994) although for many neurons, regardless of age, it acts as a neurite growth inhibitor (De Bellard et al, 1996). As an inhibitor of neurite outgrowth MAG is an important component of myelin-derived inhibitory activity, and acts on a wide variety of neuronal types (Mukhopadhay et al, 1994; Li et ai, 1996; Schafer et al, 1996; DeBellard et al, 1996). We review here the evidence that growth inhibitory molecules are an important barrier to regeneration in the CNS, and describe the characterization of MAG as a growth inhibitory molecule. The ability of MAG to influence axon regeneration in vivo is also reviewed.