dSarm/Sarm1 Is Required for Activation of an Injury-Induced Axon Death Pathway
Top Cited Papers
- 27 July 2012
- journal article
- other
- Published by American Association for the Advancement of Science (AAAS) in Science
- Vol. 337 (6093), 481-484
- https://doi.org/10.1126/science.1223899
Abstract
Axonal and synaptic degeneration is a hallmark of peripheral neuropathy, brain injury, and neurodegenerative disease. Axonal degeneration has been proposed to be mediated by an active autodestruction program, akin to apoptotic cell death; however, loss-of-function mutations capable of potently blocking axon self-destruction have not been described. Here, we show that loss of the Drosophila Toll receptor adaptor dSarm (sterile α/Armadillo/Toll-Interleukin receptor homology domain protein) cell-autonomously suppresses Wallerian degeneration for weeks after axotomy. Severed mouse Sarm1 null axons exhibit remarkable long-term survival both in vivo and in vitro, indicating that Sarm1 prodegenerative signaling is conserved in mammals. Our results provide direct evidence that axons actively promote their own destruction after injury and identify dSarm/Sarm1 as a member of an ancient axon death signaling pathway.Keywords
This publication has 31 references indexed in Scilit:
- Wallerian Degeneration, WldS, and NmnatAnnual Review of Neuroscience, 2010
- A dual leucine kinase–dependent axon self-destruction program promotes Wallerian degenerationNature Neuroscience, 2009
- The proapoptotic proteins Bax and Bak are not involved in Wallerian degenerationCell Death & Differentiation, 2003
- Axon pathology in neurological disease: a neglected therapeutic targetTrends in Neurosciences, 2002
- Axonal Self-Destruction and NeurodegenerationScience, 2002
- Wallerian degeneration of injured axons and synapses is delayed by a Ube4b/Nmnat chimeric geneNature Neuroscience, 2001
- Neurites Can Remain Viable after Destruction of the Neuronal Soma by Programmed Cell Death (Apoptosis)Developmental Biology, 1994
- Prolonged survival of transected nerve fibres in C57BL/Ola mice is an intrinsic characteristic of the axonJournal of Neurocytology, 1993
- Absence of Wallerian Degeneration does not Hinder Regeneration in Peripheral NerveEuropean Journal of Neuroscience, 1989
- XX. Experiments on the section of the glossopharyngeal and hypoglossal nerves of the frog, and observations of the alterations produced thereby in the structure of their primitive fibresPhilosophical Transactions of the Royal Society of London, 1850