AMPK controls the regenerative programme of DRG sensory neurons after injury

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dc.contributor.advisor Di Giovanni, Simone (Prof. Dr.)
dc.contributor.author Kong, Guiping
dc.date.accessioned 2018-06-15T07:29:41Z
dc.date.available 2018-06-15T07:29:41Z
dc.date.issued 2020-04-26
dc.identifier.other 1696293286 de_DE
dc.identifier.uri http://hdl.handle.net/10900/82767
dc.identifier.uri http://nbn-resolving.de/urn:nbn:de:bsz:21-dspace-827671 de_DE
dc.identifier.uri http://dx.doi.org/10.15496/publikation-24158
dc.description.abstract Regeneration after injury occurs in axons that lie in the peripheral nervous system but it fails in the central nervous system limiting functional recovery. Despite recent progress, to date we ignore the molecular identity of peripheral versus central projecting axons that might underpin this differential regenerative ability. To fill this knowledge gap, here we combined axoplasmic proteomics from sciatic or centrally projecting branches of L4-6 DRG with RNAseq to compare axonal and cell body responses between a regeneration-incompetent central spinal versus regeneration-competent peripheral sciatic nerve injury. This allowed identifying for the first time signalling pathways uniquely represented in peripheral versus central projecting L4- 6 DRG axons, including prior and subsequent to an injury. Next, RNAseq and proteomics network and pathway analysis suggested AMPK as master regulator controlling axonal regenerative signalling pathways. AMPK immunoprecipitation followed by mass spectrometry from DRG suggested that the 26S proteasome and the 26S regulatory subunit PSMC5 are preferentially bound to AMPKα for proteosomal degradation following sciatic axotomy. Mechanistically, we found that phosphorylation of proteosomal subunit PSMC5 and injury activated CaMKIIα are required for AMPKα1 degradation after sciatic injury. Moreover, ubiquitin E3 ligase Trim28 regulates AMPKα1 expression. Finally, conditional deletion of AMPKα1 promotes multiple regenerative signals, axonal regeneration and functional recovery of sensory axons across the injured spinal cord, suggesting inhibition of AMPK as novel regenerative target following spinal injury. en
dc.language.iso en de_DE
dc.publisher Universität Tübingen de_DE
dc.rights ubt-podok de_DE
dc.rights.uri http://tobias-lib.uni-tuebingen.de/doku/lic_mit_pod.php?la=de de_DE
dc.rights.uri http://tobias-lib.uni-tuebingen.de/doku/lic_mit_pod.php?la=en en
dc.subject.classification Regeneration de_DE
dc.subject.ddc 500 de_DE
dc.subject.ddc 570 de_DE
dc.subject.other Spinal cord injury en
dc.subject.other AMPK de_DE
dc.subject.other Neuron de_DE
dc.subject.other Rückenmarksverletzung de_DE
dc.title AMPK controls the regenerative programme of DRG sensory neurons after injury en
dc.type PhDThesis de_DE
dcterms.dateAccepted 2018-04-17
utue.publikation.fachbereich Medizin de_DE
utue.publikation.fakultaet 4 Medizinische Fakultät de_DE

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