Axonal transport defects and neurodegeneration: Molecular mechanisms and therapeutic implications

Because of the extremely polarized morphology, the proper functioning of neurons largely relies on the efficient cargo transport along the axon. Axonal transport defects have been reported in multiple neurodegenerative diseases as an early pathological feature. The discovery of mutations in human genes involved in the transport machinery provide a direct causative relationship between axonal transport defects and neurodegeneration. Here, we summarize the current genetic findings related to axonal transport in neurodegenerative diseases, and we discuss the relationship between axonal transport defects and other pathological changes observed in neurodegeneration. In addition, we summarize the therapeutic approaches targeting the axonal transport machinery in studies of neurodegenerative diseases. Finally, we review the technical advances in tracking axonal transport both in vivo and in vitro.