Schwann cell-axon interactions in Charcot-Marie-Tooth disease

The consequences of the molecular defects in myelin genes are manifest from the time of birth in most patients, as assessed either electrodiagnostically or pathologically. Reduction in nerve conduction velocity is present from the first weeks of life, but the clinical manifestations have been recognized as predominantly distal and dominated by distal muscle atrophy. The recent advances in understanding the molecular defects involved present a paradox: the molecular abnormalities are found in intrinsic Schwann cell proteins, not in distal axons. Thus, the interactions between Schwann cells and axons have been the focus of much attention. Here, we present findings on the effects of Schwann cell phenotype on the exon and how abnormalities in myelin alter the axonal cytoskeleton. The clinical importance of Schwann cell-axon interactions extends beyond Charcot-Marie-Tooth disorders. The same principles may apply in the CNS, for example, in multiple sclerosis.