Wallerian Degeneration in Injury and Diseases: Concepts and Prevention

The axon is a highly specialized compartment of neurons. Besides their basic function connecting neurons to their targets, axons play key roles in the nervous system. They are involved in the transport of several molecules indispensable to neuronal activity, act as sensors to guidance cues during development and regeneration, and are essential to maintain normal glial cell functions and myelin sheath assembly (Nave & Trap 2008). Recent evidence indicates that mRNA and Schwann cells-delivered ribosomes can be found within the axoplasm, suggesting that axons may be capable of synthesizing specific proteins (Court et al., 2008). However, most axonal structural proteins are synthesized in the neuronal cell body and transported along the length of the axon. Interruption of this supply leads to a degenerative process known as Wallerian degeneration (WD) in the distal portion of the axon (Coleman, 2005). WD is triggered by intrinsic degenerative pathways that are not correlated to cellular apoptosis (Finn et al., 2000). Axon degeneration is a final common pathway observed not only after a traumatic nerve injury, but also in many neurodegenerative disorders (e.g., Parkinson`s and Alzheimer`s diseases) and in demyelinating diseases such as multiple sclerosis (Coleman, 2005; Coleman & Freeman, 2010). Uncovering the mechanisms that trigger and control axon degeneration is extremely relevant, as such knowledge may offer novel tools to treat severed or damaged axons as well as several neurodegenerative disorders in which WD takes place. In this chapter, we will review the basic concepts of WD, with emphasis on the mechanisms that control axon degeneration following trauma. Next, we will address the issue whether or not current antidegenerative strategies are efficient and can be envisioned to be applied to humans in the near future.