WldS, Nmnats and axon degeneration-progress in the past two decades

Abstract

A chimeric protein called Wallerian degeneration slow (Wld S ) was first discovered in a spontaneous mutant strain of mice that exhibited delayed Wallerian degeneration. This provides a useful tool in elucidating the mechanisms of axon degeneration. Over-expression of Wld S attenuates the axon degeneration that is associated with several neurodegenerative disease models, suggesting a new logic for developing a potential protective strategy. At molecular level, although Wld S is a fusion protein, the nicotinamide mononucleotide adenylyl transferase 1 (Nmnat1) is required and sufficient for the protective effects of Wld S , indicating a critical role of NAD biosynthesis and perhaps energy metabolism in axon degeneration. These findings challenge the proposed model in which axon degeneration is operated by an active programmed process and thus may have important implication in understanding the mechanisms of neurodegeneration. In this review, we will summarize these recent findings and discuss their relevance to the mechanisms of axon degeneration.

Overexpression of Wlds or Nmnat2 in mauthner cells by single‐cell electroporation delays axon degeneration in live zebrafish

“…The in vivo protective effect of the Wld S protein has also been demonstrated in different species, such as rat and Drosophila (Feng et al, 2010). Additionally, the cation of the percentage of remaining distal axons before (0 hr) and after lesion (32 or 52 hr).…”

Axon degeneration in Parkinson's disease

“…This mutation arose spontaneously in C57Bl/6 mice, and it was demonstrated to cause delayed Wallerian degeneration in peripheral nerve after axotomy (Lunn et al, 1989). Wld S can delay axonal degeneration about ten-fold from a wide variety of genetic and toxin-inducing stimuli both in vivo and in vitro (Coleman and Freeman, 2010, Feng et al, 2010). Wld S is a chimeric protein composed of the N-terminal 70 amino acids of the ubiquitination factor Ube4b followed by a 18 amino acid linker region and the entire sequence of Nmnat1, a key enzyme in the biosynthesis of NAD + (Mack et al, 2001).…”

Novel cryoneurolysis device for the treatment of sensory and motor peripheral nerves

“…Upon injury, the axon begins a degeneration process at the injury site and progresses distally. Morphologically, this process is characterized by a beading appearance followed by granular disintegration of the axons at, and distal to, the site of exposure [14]. Concurrently, the myelin sheath undergoes a degeneration phase, and the macrophages and Schwann cells function to clear the cellular debris.…”