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000141516 0247_ $$2doi$$a10.1016/j.neuron.2019.07.007
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000141516 0247_ $$2pmc$$apmc:PMC6763392
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000141516 0247_ $$2ISSN$$a1097-4199
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000141516 037__ $$aDZNE-2020-07840
000141516 041__ $$aEnglish
000141516 082__ $$a610
000141516 1001_ $$0P:(DE-2719)2810470$$aTedeschi, Andrea$$b0
000141516 245__ $$aADF/Cofilin-Mediated Actin Turnover Promotes Axon Regeneration in the Adult CNS.
000141516 260__ $$aNew York, NY$$bElsevier$$c2019
000141516 264_1 $$2Crossref$$3print$$bElsevier BV$$c2019-09-01
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000141516 520__ $$aInjured axons fail to regenerate in the adult CNS, which contrasts with their vigorous growth during embryonic development. We explored the potential of re-initiating axon extension after injury by reactivating the molecular mechanisms that drive morphogenetic transformation of neurons during development. Genetic loss- and gain-of-function experiments followed by time-lapse microscopy, in vivo imaging, and whole-mount analysis show that axon regeneration is fueled by elevated actin turnover. Actin depolymerizing factor (ADF)/cofilin controls actin turnover to sustain axon regeneration after spinal cord injury through its actin-severing activity. This pinpoints ADF/cofilin as a key regulator of axon growth competence, irrespective of developmental stage. These findings reveal the central role of actin dynamics regulation in this process and elucidate a core mechanism underlying axon growth after CNS trauma. Thereby, neurons maintain the capacity to stimulate developmental programs during adult life, expanding their potential for plasticity. Thus, actin turnover is a key process for future regenerative interventions.
000141516 536__ $$0G:(DE-HGF)POF3-341$$a341 - Molecular Signaling (POF3-341)$$cPOF3-341$$fPOF III$$x0
000141516 536__ $$0G:(DE-HGF)POF3-342$$a342 - Disease Mechanisms and Model Systems (POF3-342)$$cPOF3-342$$fPOF III$$x1
000141516 542__ $$2Crossref$$i2019-09-01$$uhttps://www.elsevier.com/tdm/userlicense/1.0/
000141516 542__ $$2Crossref$$i2020-09-25$$uhttp://www.elsevier.com/open-access/userlicense/1.0/
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000141516 650_2 $$2MeSH$$aActins: metabolism
000141516 650_2 $$2MeSH$$aAnimals
000141516 650_2 $$2MeSH$$aAxons: metabolism
000141516 650_2 $$2MeSH$$aAxons: pathology
000141516 650_2 $$2MeSH$$aCofilin 1: genetics
000141516 650_2 $$2MeSH$$aCofilin 1: metabolism
000141516 650_2 $$2MeSH$$aCofilin 2: genetics
000141516 650_2 $$2MeSH$$aCofilin 2: metabolism
000141516 650_2 $$2MeSH$$aDestrin: genetics
000141516 650_2 $$2MeSH$$aDestrin: metabolism
000141516 650_2 $$2MeSH$$aGrowth Cones: metabolism
000141516 650_2 $$2MeSH$$aGrowth Cones: pathology
000141516 650_2 $$2MeSH$$aIntravital Microscopy
000141516 650_2 $$2MeSH$$aMice
000141516 650_2 $$2MeSH$$aMicroscopy, Confocal
000141516 650_2 $$2MeSH$$aNerve Regeneration: genetics
000141516 650_2 $$2MeSH$$aNeurons: metabolism
000141516 650_2 $$2MeSH$$aNeurons: pathology
000141516 650_2 $$2MeSH$$aRats
000141516 650_2 $$2MeSH$$aSpinal Cord Injuries: genetics
000141516 650_2 $$2MeSH$$aSpinal Cord Injuries: metabolism
000141516 650_2 $$2MeSH$$aSpinal Cord Injuries: pathology
000141516 650_2 $$2MeSH$$aTime-Lapse Imaging
000141516 7001_ $$0P:(DE-2719)2810386$$aDupraz, Sebastian$$b1
000141516 7001_ $$0P:(DE-2719)2811540$$aCurcio, Michele$$b2
000141516 7001_ $$0P:(DE-2719)2810278$$aLaskowski, Claudia J$$b3
000141516 7001_ $$0P:(DE-2719)2811123$$aSchaffran, Barbara$$b4
000141516 7001_ $$0P:(DE-2719)2810272$$aFlynn, Kevin C$$b5
000141516 7001_ $$0P:(DE-2719)2810952$$aDa Silva Santos, Telma$$b6$$udzne
000141516 7001_ $$0P:(DE-2719)2810277$$aStern, Sina$$b7
000141516 7001_ $$0P:(DE-2719)2812271$$aHilton, Brett J$$b8
000141516 7001_ $$aLarson, Molly J E$$b9
000141516 7001_ $$aGurniak, Christine B$$b10
000141516 7001_ $$aWitke, Walter$$b11
000141516 7001_ $$0P:(DE-2719)2810270$$aBradke, Frank$$b12$$eFirst author
000141516 77318 $$2Crossref$$3journal-article$$a10.1016/j.neuron.2019.07.007$$b : Elsevier BV, 2019-09-01$$n6$$p1073-1085.e6$$tNeuron$$v103$$x0896-6273$$y2019
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000141516 8564_ $$uhttps://www.sciencedirect.com/science/article/pii/S0896627319306336
000141516 8567_ $$2Pubmed Central$$uhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC6763392
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