The Fast and the Furious: Axonal Transport Defects in Sickness, Injury and Aging

Intracellular transport within long, small caliber axons is essential for the homeostasis of the neuron as well as to the health of the neuronal network. Emerging work has implicated that defects in this long distance axonal transport pathway causes neurodegeneration and death, and defects in transport has been implicated in aging, but little is known about the mechanistic details of how transport defects lead to degeneration and death. Work has shown that essential components and many proteins involved in disease (amyloid precursor protein-APP, huntingtin-HTT, a-synuclein, superoxide dismutase 1 SOD-1, etc) are packaged into vesicular complexes and moved down the axon. However, the identity of these cargo complexes and the components that they carry are unknown. The formation of these numerous cargo packages and how their motility is regulated due to specific cues is also not well known. While there is evidence for the presence of RNA in axons and synapses, whether activation of RNA transport is a mechanism for synapse function, repair or regeneration is unclear. Further, stress and injury activate signaling complexes that modify intracellular dynamics, but the mechanisms governing this activation, the regulatory cues that initiate the movement of signaling components, the packaging of “recovery components” and their role in repair and regeneration are ambiguous. Age dependent defects in mitochondrial and organelle transport have also been reported, but the mechanisms of these processes are unclear. The susceptibility of the axonal transport pathway to mechanical injury (traumatic brain injury) is a novel area unraveling the consequences of transport defects in consciousness. Therefore, the collective understanding of the relationship axonal transport plays in sickness, injury and aging enables the development of effective therapeutics to an essential pathway that has potential applicability for treatment for many human conditions.

This Research Topic aims to address unanswered areas in sickness, injury and aging due to defects in intracellular transport; highlighting recent progress using in vivo and in vitro approaches, cutting edge imaging techniques and “omic” technologies (genomics, transcriptomics, proteomics), in addition to biochemical, molecular, physiological strategies. This research topic will not only shed light on the functional mechanics of the long distance transport pathway within axons giving insight as to how sustained transport is essential for the health of the neuron and the neuronal networks in a working brain, but will also explore how defects in this pathway can be abolished, enabling the development of effective treatments. Any type of contribution; original research, review, or perspective on this topic are welcome.