Editorial: Pathways and Processes Underpinning Axonal Biology and Pathobiology

Neurons are highly polarized cells with axons that can extend beyond a meter. Axons provide long-range connections between somas and target cells, permitting rapid electrical communication. Given these distances, axons require a continuous supply of organelles, mRNAs, and proteins. This is achieved through bi-directional cargo trafficking along microtubules by motor proteins in the process of axonal transport; however, in vivo axonal transport rates are well below 10 μm/s (Tosolini et al., 2021), thus additional mechanisms are required for distal axons to efficiently respond to environmental stimuli. Consequently, local translation of readily-available transcripts provides an important mechanism to overcome distance constraints and allow proteome modification (Dalla Costa et al., 2021). Nevertheless, these vital processes are not independent since mRNA must travel from the nucleus to translation sites. In fact, transport and translation are intricately linked through a process called “hitchhiking,” whereby mRNAs are co-transported with organelles through tethering of RNA-binding proteins (RBPs) for on-demand axonal translation (Vargas et al., 2022). Accordingly, disruption of transport or translation in axons can impair neurodevelopment and drive neurodegeneration (Costa and Willis, 2018; Sleigh et al., 2019). Nonetheless, despite recent developments in axon-specific methods (Farias et al., 2019; Surana et al., 2020), it is often unclear whether perturbations are a cause or consequence of neurodegeneration.

With this special issue, we aim to showcase recent advances in axon biology to stimulate a field poised to generate a comprehensive understanding of pathways and processes critical to axonal integrity. We present ten articles covering themes of transport/translation, degeneration, and nerve injury/regeneration.