This lecture will be divided into two topics. First will focus on axon degeneration. Axons of the PNS undergo a stereotypic response to traumatic injury called Wallerian degeneration. This process shares many of the characteristics of distal axonal degeneration seen in peripheral neuropathies. The molecular mechanisms that underlie the Wallerian degeneration are being uncovered and some of these such as NMNAT, DLK and Sarm1 also play an important role in peripheral neuropathies. These molecular pathways offer potential therapeutic targets to treat or prevent peripheral neuropathies. The second part of the lecture will focus on axon regeneration and challenges that human nerve regeneration poses, including slow rate of regeneration that is intrinsically controlled by the neuron, the chronic denervation changes that occur in the glial environment that impedes regeneration with proximal injuries and chronic denervation changes that occur in target tissues that prevent functional recovery.
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