Wallerian degeneration refers to the changes that take place in the distal segment, which is separated from the cell body, when the axon of a neuron is transected. This chapter discusses wallerian degeneration and proposes new avenues of research that can improve the understanding of multiple sclerosis as a neuronal disease. The wallerian degeneration is an active process that requires the presence and activation of a cellular pathway that regulates the dissolution of the axoplasm. This cellular pathway is similar to the pathway that regulates apoptotic cell death in the sense that both are regulated active processes requiring energy, but there are significant differences too. The molecular characters that play a role in this active self-destruct mechanism are not well understood, but are different from those involved in apoptosis. The role of calcium and calcium-dependent proteases, ubiquitin proteasome system, and caspases in wallerian degeneration is also discussed. Better understanding of the molecular mechanisms of specific activation of microglia and myelin removal after axonal injury in the central nervous system (CNS) is likely to yield new therapeutic opportunities for the treatment of illnesses such as multiple sclerosis.
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