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http://purl.uniprot.org/citations/35110388http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/35110388http://www.w3.org/2000/01/rdf-schema#comment"We previously reported that a-disintegrin and metalloproteinase (ADAM)17 is a key protease regulating myelin formation. We now describe a role for ADAM17 during the Wallerian degeneration (WD) process. Unexpectedly, we observed that glial ADAM17, by regulating p75NTR processing, cell autonomously promotes remyelination, while neuronal ADAM17 is dispensable. Accordingly, p75NTR abnormally accumulates specifically when ADAM17 is maximally expressed leading to a downregulation of tissue plasminogen activator (tPA) expression, excessive fibrin accumulation over time, and delayed remyelination. Mutant mice also present impaired macrophage recruitment and defective nerve conduction velocity (NCV). Thus, ADAM17 expressed in Schwann cells, controls the whole WD process, and its absence hampers effective nerve repair. Collectively, we describe a previously uncharacterized role for glial ADAM17 during nerve regeneration. Based on the results of our study, we posit that, unlike development, glial ADAM17 promotes remyelination through the regulation of p75NTR-mediated fibrinolysis.SIGNIFICANCE STATEMENT The α-secretase a-disintegrin and metalloproteinase (ADAM)17, although relevant for developmental PNS myelination, has never been investigated in Wallerian degeneration (WD). We now unravel a new mechanism of action for this protease and show that ADAM17 cleaves p75NTR, regulates fibrin clearance, and eventually fine-tunes remyelination. The results presented in this study provide important insights into the complex regulation of remyelination following nerve injury, identifying in ADAM17 and p75NTR a new signaling axis implicated in these events. Modulation of this pathway could have important implications in promoting nerve remyelination, an often-inefficient process, with the aim of restoring a functional axo-glial unit."xsd:string
http://purl.uniprot.org/citations/35110388http://purl.org/dc/terms/identifier"doi:10.1523/jneurosci.1341-21.2022"xsd:string
http://purl.uniprot.org/citations/35110388http://purl.uniprot.org/core/author"Quattrini A."xsd:string
http://purl.uniprot.org/citations/35110388http://purl.uniprot.org/core/author"Podini P."xsd:string
http://purl.uniprot.org/citations/35110388http://purl.uniprot.org/core/author"Taveggia C."xsd:string
http://purl.uniprot.org/citations/35110388http://purl.uniprot.org/core/author"Del Carro U."xsd:string
http://purl.uniprot.org/citations/35110388http://purl.uniprot.org/core/author"Pellegatta M."xsd:string
http://purl.uniprot.org/citations/35110388http://purl.uniprot.org/core/author"Forese M.G."xsd:string
http://purl.uniprot.org/citations/35110388http://purl.uniprot.org/core/author"Canevazzi P."xsd:string
http://purl.uniprot.org/citations/35110388http://purl.uniprot.org/core/author"Valenzano S."xsd:string
http://purl.uniprot.org/citations/35110388http://purl.uniprot.org/core/date"2022"xsd:gYear
http://purl.uniprot.org/citations/35110388http://purl.uniprot.org/core/name"J Neurosci"xsd:string
http://purl.uniprot.org/citations/35110388http://purl.uniprot.org/core/pages"2433-2447"xsd:string
http://purl.uniprot.org/citations/35110388http://purl.uniprot.org/core/title"ADAM17 Regulates p75NTR-Mediated Fibrinolysis and Nerve Remyelination."xsd:string
http://purl.uniprot.org/citations/35110388http://purl.uniprot.org/core/volume"42"xsd:string
http://purl.uniprot.org/citations/35110388http://www.w3.org/2004/02/skos/core#exactMatchhttp://purl.uniprot.org/pubmed/35110388
http://purl.uniprot.org/citations/35110388http://xmlns.com/foaf/0.1/primaryTopicOfhttps://pubmed.ncbi.nlm.nih.gov/35110388
http://purl.uniprot.org/uniprot/#_B2RRI1-mappedCitation-35110388http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/35110388
http://purl.uniprot.org/uniprot/#_B2RRI4-mappedCitation-35110388http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/35110388
http://purl.uniprot.org/uniprot/#_E9PXU2-mappedCitation-35110388http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/35110388
http://purl.uniprot.org/uniprot/#_B7ZNJ0-mappedCitation-35110388http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/35110388
http://purl.uniprot.org/uniprot/#_J3QMF2-mappedCitation-35110388http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/35110388
http://purl.uniprot.org/uniprot/#_Q3UV09-mappedCitation-35110388http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/35110388
http://purl.uniprot.org/uniprot/#_Q3UNK7-mappedCitation-35110388http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/35110388