title: The purine nucleosides adenosine and guanosine delay axonal degeneration in vitro.
abstract: Axonal degeneration is a key component of many neurodegenerative diseases. Injured axons undergo a program of self-destruction termed Wallerian degeneration that is an active, well-regulated process. The pathways leading to axon fragmentation are uncharacterized, but experiments with wld(s) mutant mice led to the discovery that over-expression of NMN adenylyltransferase 1 or treatment with NAD(+) can inhibit axonal degeneration. In this study, we show that the purine nucleosides adenosine and guanosine, but not inosine, inhibit injury-induced axonal degeneration in cultured dorsal root ganglia neurons. Axons can be preserved by adding adenosine within 6 h of the axonal injury. The presence of adenosine was required continuously after the injury to maintain axonal protection. Together these results suggest that adenosine does not alter the neuronal response to injury, but instead inhibits a local axonal pathway necessary for the commitment and/or execution of the axon destructive program.
authors.affiliation: Department of Pathology, Hope Center for Neurological Disorders, Washington University School of Medicine, St Louis, Missouri, USA.
authors.forename: Craig
authors.initials: C
authors.lastname: Press
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Milbrandt
mesh_terms: D000241:Adenosine / Q000502:physiology* / Q000627:therapeutic use; D000818:Animals; D001369:Axons / Q000187:drug effects* / Q000473:pathology; D002478:Cells, Cultured; D005727:Ganglia, Spinal / Q000187:drug effects / Q000473:pathology; D006151:Guanosine / Q000502:physiology* / Q000627:therapeutic use; D051379:Mice; D009410:Nerve Degeneration / Q000188:drug therapy / Q000473:pathology* / Q000517:prevention & control*; D011684:Purine Nucleosides / Q000502:physiology / Q000627:therapeutic use; D014855:Wallerian Degeneration / Q000188:drug therapy / Q000473:pathology
chemical_list: D011684:Purine Nucleosides; D006151:Guanosine; D000241:Adenosine