Nogo-A, a potent inhibitor of neurite outgrowth and regeneration

The lack of regrowth of injured neurons in the adult central nervous system (CNS) of higher vertebrates was accepted as a fact for many decades. In th e last few years a very different view emerged; regeneration of lesioned fi bre tracts in vivo could be induced experimentally, and molecules that are responsible for inhibition and repulsion of growing neurites have been defi ned. Mechanisms that link cellular phenomena like growth cone turning or gr owth cone collapse to intracellular changes in second messenger systems and cytoskeletal dynamics became unveiled. This article reviews recent develop ments in this field, focusing especially on one of the best characterised n eurite outgrowth inhibitory molecules found in CNS myelin that was recently cloned: Nogo-A. Nogo-A is a high molecular weight transmembrane protein an d an antigen of the monoclonal antibody mAb IN-1 that was shown to promote long-distance regeneration and functional recovery in vivo when applied to spinal cord-injured adult rats. Nogo-A is expressed by oligodendrocytes in white matter of the CNS, With the molecular characterisation of this factor new possibilities open up to achieve structural and functional repair of t he injured CNS.