Axonal Transport Disorders

Because neurons possess the most complex geometries of any cell type, intracellular transport systems are essential to deliver critical proteins to specific anatomical and functional sites (e.g., dendrites, axons, and synaptic terminals) where relatively few proteins are synthesized. Although increasing evidence suggests that some proteins are synthesized locally within dendrites and spines and even within axons/terminals, the principal sites of neuronal protein synthesis are the cell bodies; axons and nerve terminals, in particular, depend primarily on this source for a continued supply of certain proteins to perform normal functions. The axonal transport systems, which evolved to deliver essential materials to the most distal parts of nerve cells, participate in the delivery of proteins and prepackaged cargo to specific destinations. These systems were initially distinguished based on velocity (fast, intermediate, or slow) and direction of movement (anterograde and retrograde). The identification of anterograde and retrograde transport motors and delineation of transport vesicles and cargo are critical players in this evolving story of discovery. Because axonal transport is a critical process within nerve cells, it is not surprising that axonal transport is involved in regeneration and that impairments in transport are associated with a variety of disorders of the peripheral and central nervous systems. In this article, we describe these transport systems and discuss how axonal transport functions in regeneration and repair and how malfunctions of transport processes are implicated in both experimental models and in human disorders.