Inhibition of Axonal Regeneration*

Because axonal damage and loss are frequent phenomena of multiple sclerosis and other types of neurodegenerative diseases, and because the effects can be devastating clinically, attention has been focused on repair to axons. However, axon regeneration appears to be inhibited via a variety of possible cellular pathways and molecules. In the following article, several of these pathways are examined, including the possibility that the mature neuron loses its intrinsic capacity to regenerate due to factors associated with aging, environmental factors such as lack of neurotrophic support, and/or because some manner of inhibitory mechanisms are responsible. In the future, it may be necessary to design different therapeutic strategies for each unique situation and combine these, because it is entirely possible that a number of mechanisms are involved, and even that axons behave differently in different circumstances. (Adv Stud Med. 2005;5(4D):S409-S412) A s has previously been discussed, axonal damage and loss are frequent phenomena of multiple sclerosis and other types of neurodegenerative diseases. Because the spinal cord is a communication channel between the brain and the rest of the body, in the event of injury to either descending or ascending axons, this will impair either motor or sensory function respectively, since injured axons in the brain and spinal cord cannot regenerate easily. Upon injury, the distal part of an axon undergoes Wallerian degeneration. The proximal end of the axon quickly reseals, and reforms an elaborate structure called the growth cone, which is also present in all immature axons during development (Figure 1). In the peripheral nervous system (PNS), a lesioned axon still can reform a growth cone and regenerate back to its original targets, but that is not the case for the central nervous system (CNS). Over the years, several possibilities have been proposed to explain regeneration failure in the mature CNS. These include: the possibility that the mature neuron loses its intrinsic capacity to regenerate due to factors associated with aging, environmental contributions such as lack of neurotrophic support, and/or that some manner of inhibitory mechanisms are responsible.