Abstract
Reactive oxygen species (ROS) contribute to tissue damage and remodelling mediated by the inflammatory response after injury. Here we show that ROS, which promote axonal dieback and degeneration after injury, are also required for axonal regeneration and functional recovery after spinal injury. We find that ROS production in the injured sciatic nerve and dorsal root ganglia requires CX3CR1-dependent recruitment of inflammatory cells. Next, exosomes containing functional NADPH oxidase 2 complexes are released from macrophages and incorporated into injured axons via endocytosis. Once in axonal endosomes, active NOX2 is retrogradely transported to the cell body through an importin-β1-dynein-dependent mechanism. Endosomal NOX2 oxidizes PTEN, which leads to its inactivation, thus stimulating PI3K-phosporylated (p-)Akt signalling and regenerative outgrowth. Challenging the view that ROS are exclusively involved in nerve degeneration, we propose a previously unrecognized role of ROS in mammalian axonal regeneration through a NOX2-PI3K-p-Akt signalling pathway.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 307-319 |
| Number of pages | 13 |
| Journal | Nature Cell Biology |
| Volume | 20 |
| Issue number | 3 |
| DOIs | |
| State | Published - Mar 1 2018 |
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- Cell Biology
Cite this
Reactive oxygen species regulate axonal regeneration through the release of exosomal NADPH oxidase 2 complexes into injured axons. / Hervera, Arnau; De Virgiliis, Francesco; Palmisano, Ilaria; Zhou, Luming; Tantardini, Elena; Kong, Guiping; Hutson, Thomas; Danzi, Matt C.; Perry, Rotem Ben Tov; Santos, Celio X.C.; Kapustin, Alexander N.; Fleck, Roland A.; Del Río, José Antonio; Carroll, Thomas; Lemmon, Vance; Bixby, John; Shah, Ajay M.; Fainzilber, Mike; Di Giovanni, Simone.
In: Nature Cell Biology, Vol. 20, No. 3, 01.03.2018, p. 307-319.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Reactive oxygen species regulate axonal regeneration through the release of exosomal NADPH oxidase 2 complexes into injured axons
AU - Hervera, Arnau
AU - De Virgiliis, Francesco
AU - Palmisano, Ilaria
AU - Zhou, Luming
AU - Tantardini, Elena
AU - Kong, Guiping
AU - Hutson, Thomas
AU - Danzi, Matt C.
AU - Perry, Rotem Ben Tov
AU - Santos, Celio X.C.
AU - Kapustin, Alexander N.
AU - Fleck, Roland A.
AU - Del Río, José Antonio
AU - Carroll, Thomas
AU - Lemmon, Vance
AU - Bixby, John
AU - Shah, Ajay M.
AU - Fainzilber, Mike
AU - Di Giovanni, Simone
PY - 2018/3/1
Y1 - 2018/3/1
N2 - Reactive oxygen species (ROS) contribute to tissue damage and remodelling mediated by the inflammatory response after injury. Here we show that ROS, which promote axonal dieback and degeneration after injury, are also required for axonal regeneration and functional recovery after spinal injury. We find that ROS production in the injured sciatic nerve and dorsal root ganglia requires CX3CR1-dependent recruitment of inflammatory cells. Next, exosomes containing functional NADPH oxidase 2 complexes are released from macrophages and incorporated into injured axons via endocytosis. Once in axonal endosomes, active NOX2 is retrogradely transported to the cell body through an importin-β1-dynein-dependent mechanism. Endosomal NOX2 oxidizes PTEN, which leads to its inactivation, thus stimulating PI3K-phosporylated (p-)Akt signalling and regenerative outgrowth. Challenging the view that ROS are exclusively involved in nerve degeneration, we propose a previously unrecognized role of ROS in mammalian axonal regeneration through a NOX2-PI3K-p-Akt signalling pathway.
AB - Reactive oxygen species (ROS) contribute to tissue damage and remodelling mediated by the inflammatory response after injury. Here we show that ROS, which promote axonal dieback and degeneration after injury, are also required for axonal regeneration and functional recovery after spinal injury. We find that ROS production in the injured sciatic nerve and dorsal root ganglia requires CX3CR1-dependent recruitment of inflammatory cells. Next, exosomes containing functional NADPH oxidase 2 complexes are released from macrophages and incorporated into injured axons via endocytosis. Once in axonal endosomes, active NOX2 is retrogradely transported to the cell body through an importin-β1-dynein-dependent mechanism. Endosomal NOX2 oxidizes PTEN, which leads to its inactivation, thus stimulating PI3K-phosporylated (p-)Akt signalling and regenerative outgrowth. Challenging the view that ROS are exclusively involved in nerve degeneration, we propose a previously unrecognized role of ROS in mammalian axonal regeneration through a NOX2-PI3K-p-Akt signalling pathway.
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UR - http://www.scopus.com/inward/citedby.url?scp=85041899028&partnerID=8YFLogxK
U2 - 10.1038/s41556-018-0039-x
DO - 10.1038/s41556-018-0039-x
M3 - Article
C2 - 29434374
AN - SCOPUS:85041899028
VL - 20
SP - 307
EP - 319
JO - Nature Cell Biology
JF - Nature Cell Biology
SN - 1465-7392
IS - 3
ER -