TY - JOUR
T1 - dSarm/Sarm1 is required for activation of an injury-induced axon death pathway
AU - Osterloh, Jeannette M.
AU - Yang, Jing
AU - Rooney, Timothy M.
AU - Fox, A. Nicole
AU - Adalbert, Robert
AU - Powell, Eric H.
AU - Sheehan, Amy E.
AU - Avery, Michelle A.
AU - Hackett, Rachel
AU - Logan, Mary A.
AU - MacDonald, Jennifer M.
AU - Ziegenfuss, Jennifer S.
AU - Milde, Stefan
AU - Hou, Ying Ju
AU - Nathan, Carl
AU - Ding, Aihao
AU - Brown, Robert H.
AU - Conforti, Laura
AU - Coleman, Michael
AU - Tessier-Lavigne, Marc
AU - Züchner, Stephan
AU - Freeman, Marc R.
PY - 2012/7/27
Y1 - 2012/7/27
N2 - 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 a/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 amember of an ancient axon death signaling pathway.
AB - 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 a/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 amember of an ancient axon death signaling pathway.
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U2 - 10.1126/science.1223899
DO - 10.1126/science.1223899
M3 - Article
C2 - 22678360
AN - SCOPUS:84864332905
SN - 0036-8075
VL - 337
SP - 481
EP - 484
JO - Science
JF - Science
IS - 6093
ER -