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AMPK controls the axonal regenerative ability of dorsal root ganglia sensory neurons after spinal cord injury.

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Kong et al. Nature Metabolism revision 17-06-20 clean file.docxAccepted version183.23 kBMicrosoft WordView/Open
Title: AMPK controls the axonal regenerative ability of dorsal root ganglia sensory neurons after spinal cord injury.
Authors: Kong, G
Zhou, L
Serger, E
Palmisano, I
De Virgiliis, F
Hutson, TH
Mclachlan, E
Freiwald, A
La Montanara, P
Shkura, K
Puttagunta, R
Di Giovanni, S
Item Type: Journal Article
Abstract: Regeneration after injury occurs in axons that lie in the peripheral nervous system but fails in the central nervous system, thereby limiting functional recovery. Differences in axonal signalling in response to injury that might underpin this differential regenerative ability are poorly characterized. Combining axoplasmic proteomics from peripheral sciatic or central projecting dorsal root ganglion (DRG) axons with cell body RNA-seq, we uncover injury-dependent signalling pathways that are uniquely represented in peripheral versus central projecting sciatic DRG axons. We identify AMPK as a crucial regulator of axonal regenerative signalling that is specifically downregulated in injured peripheral, but not central, axons. We find that AMPK in DRG interacts with the 26S proteasome and its CaMKIIα-dependent regulatory subunit PSMC5 to promote AMPKα proteasomal degradation following sciatic axotomy. Conditional deletion of AMPKα1 promotes multiple regenerative signalling pathways after central axonal injury and stimulates robust axonal growth across the spinal cord injury site, suggesting inhibition of AMPK as a therapeutic strategy to enhance regeneration following spinal cord injury.
Issue Date: 10-Aug-2020
Date of Acceptance: 26-Jun-2020
URI: http://hdl.handle.net/10044/1/81976
DOI: 10.1038/s42255-020-0252-3
ISSN: 2522-5812
Publisher: Nature Research
Start Page: 918
End Page: 933
Journal / Book Title: Nature Metabolism
Volume: 2
Copyright Statement: © The Author(s), under exclusive licence to Springer Nature Limited 2020. The final publication is available at Springer via https://doi.org/10.1038/s42255-020-0252-3
Sponsor/Funder: International Spinal Research Trust
Wings for Life Spinal Cord Research Foundation
The Weizmann Institute of Science
Funder's Grant Number: NRB111
WFL/UK/07/16
N/A
Publication Status: Published
Conference Place: Germany
Online Publication Date: 2020-08-10
Appears in Collections:Faculty of Medicine
Department of Brain Sciences