Releasing the brake: restoring fast axonal transport in neurodegenerative disorders

•Proteins involved in the transport of organelles are mutated in neurodegenerative disorders.•Deregulations of FAT occur in several neurodegenerative disorders.•Restoring FAT may slow neurodegeneration and be of therapeutic interest.

Emerging evidence suggests that the dysregulation of fast axonal transport (FAT) plays a crucial role in several neurodegenerative disorders. Some of these diseases are caused by mutations affecting the molecular motors or adaptors that mediate FAT, and transport defects in organelles such as mitochondria and vesicles are observed in most, if not all neurodegenerative disorders. The relationship between neurodegenerative disorders and FAT is probably due to the extreme polarization of neurons, which extend long processes such as axons and dendrites. These characteristics render neurons particularly sensitive to transport alterations. Here we review the impact of such alterations on neuronal survival. We also discuss various strategies that might restore FAT, potentially slowing disease progression.