title: Inhibiting poly(ADP-ribosylation) improves axon regeneration.
abstract: The ability of a neuron to regenerate its axon after injury depends in part on its intrinsic regenerative potential. Here, we identify novel intrinsic regulators of axon regeneration: poly(ADP-ribose) glycohodrolases (PARGs) and poly(ADP-ribose) polymerases (PARPs). PARGs, which remove poly(ADP-ribose) from proteins, act in injuredC. elegansGABA motor neurons to enhance axon regeneration. PARG expression is regulated by DLK signaling, and PARGs mediate DLK function in enhancing axon regeneration. Conversely, PARPs, which add poly(ADP-ribose) to proteins, inhibit axon regeneration of bothC. elegansGABA neurons and mammalian cortical neurons. Furthermore, chemical PARP inhibitors improve axon regeneration when administered after injury. Our results indicate that regulation of poly(ADP-ribose) levels is a critical function of the DLK regeneration pathway, that poly-(ADP ribosylation) inhibits axon regeneration across species, and that chemical inhibition of PARPs can elicit axon regeneration.
authors.affiliation: Department of Genetics, Yale University School of Medicine, New Haven, United States.|Department of Neuroscience, Yale University School of Medicine, New Haven, United States.|Program in Cellular Neuroscience, Neurodegeneration, and Repair, Yale University School of Medicine, New Haven, United States.
authors.forename: Alexandra B
authors.identifier: 0000-0002-7449-9188
authors.initials: AB
authors.lastname: Byrne
authors.affiliation: Department of Cell and Developmental Biology, Vanderbilt University, Nashville, United States.|Program in Neuroscience, Vanderbilt University, Nashville, United States.
authors.forename: Rebecca D
authors.initials: RD
authors.lastname: McWhirter
authors.affiliation: Program in Cellular Neuroscience, Neurodegeneration, and Repair, Yale University School of Medicine, New Haven, United States.|Department of Neurology, Yale University School of Medicine, New Haven, United States.
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Sekine
authors.affiliation: Department of Neuroscience, Yale University School of Medicine, New Haven, United States.|Program in Cellular Neuroscience, Neurodegeneration, and Repair, Yale University School of Medicine, New Haven, United States.|Department of Neurology, Yale University School of Medicine, New Haven, United States.
authors.forename: Stephen M
authors.identifier: 0000-0001-8188-3092
authors.initials: SM
authors.lastname: Strittmatter
authors.affiliation: Department of Cell and Developmental Biology, Vanderbilt University, Nashville, United States.|Program in Neuroscience, Vanderbilt University, Nashville, United States.
authors.forename: David M
authors.identifier: 0000-0001-9048-873X
authors.initials: DM
authors.lastname: Miller
authors.affiliation: Department of Genetics, Yale University School of Medicine, New Haven, United States.|Department of Neuroscience, Yale University School of Medicine, New Haven, United States.|Program in Cellular Neuroscience, Neurodegeneration, and Repair, Yale University School of Medicine, New Haven, United States.
authors.forename: Marc
authors.identifier: 0000-0002-3068-068X
authors.initials: M
authors.lastname: Hammarlund
mesh_terms: D036002:ADP Ribose Transferases / Q000378:metabolism*; D000818:Animals; D001369:Axons / Q000502:physiology*; D017173:Caenorhabditis elegans / Q000201:enzymology / Q000502:physiology; D006026:Glycoside Hydrolases / Q000378:metabolism*; D000074747:Poly ADP Ribosylation; D012038:Regeneration
chemical_list: D036002:ADP Ribose Transferases; D006026:Glycoside Hydrolases; C022407:poly ADP-ribose glycohydrolase
keywords: C. elegans; axon regeneration; dlk-1/MAPKKK; mouse; neuroscience; poly(ADP-ribose) glycohydrolase; poly(ADP-ribose) polymerase