Wallerian degeneration: an emerging axon death pathway linking injury and disease.
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.
1] School of Biomedical Sciences, University of Nottingham, Medical School, Queen's Medical Centre, Nottingham, NG7 2UH, UK. [2].
Laura
L
Conforti
1] The Babraham Institute, Babraham Research Campus, Babraham, Cambridge, CB22 3AT, UK. [2].
Jonathan
J
Gilley
The Babraham Institute, Babraham Research Campus, Babraham, Cambridge, CB22 3AT, UK.
Michael P
MP
Coleman
D000818:Animals; D051186:Armadillo Domain Proteins / Q000235:genetics / Q000378:metabolism; D001369:Axons / Q000502:physiology*; D016923:Cell Death / Q000502:physiology; D003598:Cytoskeletal Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D009434:Neural Pathways / Q000473:pathology; D009474:Neurons / Q000473:pathology*; D009612:Nicotinamide-Nucleotide Adenylyltransferase / Q000235:genetics / Q000378:metabolism; D014855:Wallerian Degeneration / Q000235:genetics / Q000473:pathology* / Q000503:physiopathology*
D051186:Armadillo Domain Proteins; D003598:Cytoskeletal Proteins; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; C417163:PLEKHB1 protein, human; C435689:SARM1 protein, human; C484008:NMNAT2 protein, human; D009612:Nicotinamide-Nucleotide Adenylyltransferase