Ndel1 promotes axon regeneration via intermediate filaments.

Failure of axons to regenerate following acute or chronic neuronal injury is attributed to both the inhibitory glial environment and deficient intrinsic ability to re-grow. However, the underlying mechanisms of the latter remain unclear. In this study, we have investigated the role of the mammalian...

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Main Authors: Cory Toth, Su Yeon Shim, Jian Wang, Yulan Jiang, Gernot Neumayer, Camille Belzil, Wei-Qiao Liu, Jose Martinez, Douglas Zochodne, Minh Dang Nguyen
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2008-01-01
Series:PLoS ONE
Online Access:http://europepmc.org/articles/PMC2291557?pdf=render
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author Cory Toth
Su Yeon Shim
Jian Wang
Yulan Jiang
Gernot Neumayer
Camille Belzil
Wei-Qiao Liu
Jose Martinez
Douglas Zochodne
Minh Dang Nguyen
author_facet Cory Toth
Su Yeon Shim
Jian Wang
Yulan Jiang
Gernot Neumayer
Camille Belzil
Wei-Qiao Liu
Jose Martinez
Douglas Zochodne
Minh Dang Nguyen
author_sort Cory Toth
collection DOAJ
description Failure of axons to regenerate following acute or chronic neuronal injury is attributed to both the inhibitory glial environment and deficient intrinsic ability to re-grow. However, the underlying mechanisms of the latter remain unclear. In this study, we have investigated the role of the mammalian homologue of aspergillus nidulans NudE, Ndel1, emergently viewed as an integrator of the cytoskeleton, in axon regeneration. Ndel1 was synthesized de novo and upregulated in crushed and transected sciatic nerve axons, and, upon injury, was strongly associated with neuronal form of the intermediate filament (IF) Vimentin while dissociating from the mature neuronal IF (Neurofilament) light chain NF-L. Consistent with a role for Ndel1 in the conditioning lesion-induced neurite outgrowth of Dorsal Root Ganglion (DRG) neurons, the long lasting in vivo formation of the neuronal Ndel1/Vimentin complex was associated with robust axon regeneration. Furthermore, local silencing of Ndel1 in transected axons by siRNA severely reduced the extent of regeneration in vivo. Thus, Ndel1 promotes axonal regeneration; activating this endogenous repair mechanism may enhance neuroregeneration during acute and chronic axonal degeneration.
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spelling doaj.art-b6cedbbd89604537830a3c45a92242562022-12-22T03:48:15ZengPublic Library of Science (PLoS)PLoS ONE1932-62032008-01-0134e201410.1371/journal.pone.0002014Ndel1 promotes axon regeneration via intermediate filaments.Cory TothSu Yeon ShimJian WangYulan JiangGernot NeumayerCamille BelzilWei-Qiao LiuJose MartinezDouglas ZochodneMinh Dang NguyenFailure of axons to regenerate following acute or chronic neuronal injury is attributed to both the inhibitory glial environment and deficient intrinsic ability to re-grow. However, the underlying mechanisms of the latter remain unclear. In this study, we have investigated the role of the mammalian homologue of aspergillus nidulans NudE, Ndel1, emergently viewed as an integrator of the cytoskeleton, in axon regeneration. Ndel1 was synthesized de novo and upregulated in crushed and transected sciatic nerve axons, and, upon injury, was strongly associated with neuronal form of the intermediate filament (IF) Vimentin while dissociating from the mature neuronal IF (Neurofilament) light chain NF-L. Consistent with a role for Ndel1 in the conditioning lesion-induced neurite outgrowth of Dorsal Root Ganglion (DRG) neurons, the long lasting in vivo formation of the neuronal Ndel1/Vimentin complex was associated with robust axon regeneration. Furthermore, local silencing of Ndel1 in transected axons by siRNA severely reduced the extent of regeneration in vivo. Thus, Ndel1 promotes axonal regeneration; activating this endogenous repair mechanism may enhance neuroregeneration during acute and chronic axonal degeneration.http://europepmc.org/articles/PMC2291557?pdf=render
spellingShingle Cory Toth
Su Yeon Shim
Jian Wang
Yulan Jiang
Gernot Neumayer
Camille Belzil
Wei-Qiao Liu
Jose Martinez
Douglas Zochodne
Minh Dang Nguyen
Ndel1 promotes axon regeneration via intermediate filaments.
PLoS ONE
title Ndel1 promotes axon regeneration via intermediate filaments.
title_full Ndel1 promotes axon regeneration via intermediate filaments.
title_fullStr Ndel1 promotes axon regeneration via intermediate filaments.
title_full_unstemmed Ndel1 promotes axon regeneration via intermediate filaments.
title_short Ndel1 promotes axon regeneration via intermediate filaments.
title_sort ndel1 promotes axon regeneration via intermediate filaments
url http://europepmc.org/articles/PMC2291557?pdf=render
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