Abstract
Axon degeneration is a prominent early feature of most neurodegenerative disorders and can also be induced directly by nerve injury in a process known as Wallerian degeneration. The discovery of genetic mutations that delay Wallerian degeneration has provided insight into mechanisms underlying axon degeneration in disease. Rapid Wallerian degeneration requires the pro-degenerative molecules SARM1 and PHR1. Nicotinamide mononucleotide adenylyltransferase 2 (NMNAT2) is essential for axon growth and survival. Its loss from injured axons may activate Wallerian degeneration, whereas NMNAT overexpression rescues axons from degeneration. Here, we discuss the roles of these and other proposed regulators of Wallerian degeneration, new opportunities for understanding disease mechanisms and intriguing links between Wallerian degeneration, innate immunity, synaptic growth and cell death.
Publication types
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Research Support, Non-U.S. Gov't
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Review
MeSH terms
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Animals
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Armadillo Domain Proteins / genetics
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Armadillo Domain Proteins / metabolism
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Axons / physiology*
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Cell Death / physiology
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Cytoskeletal Proteins / genetics
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Cytoskeletal Proteins / metabolism
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Humans
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Intracellular Signaling Peptides and Proteins / genetics
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Intracellular Signaling Peptides and Proteins / metabolism
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Membrane Proteins / genetics
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Membrane Proteins / metabolism
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Neural Pathways / pathology
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Neurons / pathology*
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Nicotinamide-Nucleotide Adenylyltransferase / genetics
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Nicotinamide-Nucleotide Adenylyltransferase / metabolism
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Wallerian Degeneration / genetics
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Wallerian Degeneration / pathology*
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Wallerian Degeneration / physiopathology*
Substances
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Armadillo Domain Proteins
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Cytoskeletal Proteins
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Intracellular Signaling Peptides and Proteins
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Membrane Proteins
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PLEKHB1 protein, human
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SARM1 protein, human
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NMNAT2 protein, human
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Nicotinamide-Nucleotide Adenylyltransferase