Reactive oxygen species regulate axonal regeneration through the release of exosomal NADPH oxidase 2 complexes into injured axons - PubMed (original) (raw)
. 2018 Mar;20(3):307-319.
doi: 10.1038/s41556-018-0039-x. Epub 2018 Feb 12.
Francesco De Virgiliis 1 3 4, Ilaria Palmisano 1, Luming Zhou 3, Elena Tantardini 1, Guiping Kong 3, Thomas Hutson 1, Matt C Danzi 5, Rotem Ben-Tov Perry 6, Celio X C Santos 7, Alexander N Kapustin 7, Roland A Fleck 8, José Antonio Del Río 2 9 10, Thomas Carroll 11, Vance Lemmon 5, John L Bixby 5, Ajay M Shah 7, Mike Fainzilber 6, Simone Di Giovanni 12 13
Affiliations
- PMID: 29434374
- DOI: 10.1038/s41556-018-0039-x
Reactive oxygen species regulate axonal regeneration through the release of exosomal NADPH oxidase 2 complexes into injured axons
Arnau Hervera et al. Nat Cell Biol. 2018 Mar.
Erratum in
- Publisher Correction: Reactive oxygen species regulate axonal regeneration through the release of exosomal NADPH oxidase 2 complexes into injured axons.
Hervera A, De Virgiliis F, Palmisano I, Zhou L, Tantardini E, Kong G, Hutson T, Danzi MC, Perry RB, Santos CXC, Kapustin AN, Fleck RA, Del Río JA, Carroll T, Lemmon V, Bixby JL, Shah AM, Fainzilber M, Di Giovanni S. Hervera A, et al. Nat Cell Biol. 2018 Sep;20(9):1098. doi: 10.1038/s41556-018-0063-x. Nat Cell Biol. 2018. PMID: 29520084
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.
Comment in
- Exosomes deliver ROS for regeneration.
Krämer-Albers EM. Krämer-Albers EM. Nat Cell Biol. 2018 Mar;20(3):225-226. doi: 10.1038/s41556-018-0048-9. Nat Cell Biol. 2018. PMID: 29476149 No abstract available.
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