{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,14]],"date-time":"2026-06-14T09:42:20Z","timestamp":1781430140526,"version":"3.54.1"},"reference-count":64,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2019,9,30]],"date-time":"2019-09-30T00:00:00Z","timestamp":1569801600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Ministry of Defence","award":["RIPANE"],"award-info":[{"award-number":["RIPANE"]}]},{"DOI":"10.13039\/501100009629","name":"Fondazione Cassa Di Risparmio Di Trento E Rovereto","doi-asserted-by":"publisher","award":["Bando per giovani ricercatori coinvolti in progetti di eccellenza"],"award-info":[{"award-number":["Bando per giovani ricercatori coinvolti in progetti di eccellenza"]}],"id":[{"id":"10.13039\/501100009629","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003500","name":"Universit\u00e0 degli Studi di Padova","doi-asserted-by":"publisher","award":["DOR"],"award-info":[{"award-number":["DOR"]}],"id":[{"id":"10.13039\/501100003500","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>The activation of the G-protein coupled receptor CXCR4 by its ligand CXCL12\u03b1 is involved in a large variety of physiological and pathological processes, including the growth of B cells precursors and of motor axons, autoimmune diseases, stem cell migration, inflammation, and several neurodegenerative conditions. Recently, we demonstrated that CXCL12\u03b1 potently stimulates the functional recovery of damaged neuromuscular junctions via interaction with CXCR4. This result prompted us to test the neuroregeneration activity of small molecules acting as CXCR4 agonists, endowed with better pharmacokinetics with respect to the natural ligand. We focused on NUCC-390, recently shown to activate CXCR4 in a cellular system. We designed a novel and convenient chemical synthesis of NUCC-390, which is reported here. NUCC-390 was tested for its capability to induce the regeneration of motor axon terminals completely degenerated by the presynaptic neurotoxin \u03b1-Latrotoxin. NUCC-390 was found to strongly promote the functional recovery of the neuromuscular junction, as assayed by electrophysiology and imaging. This action is CXCR4 dependent, as it is completely prevented by AMD3100, a well-characterized CXCR4 antagonist. These data make NUCC-390 a strong candidate to be tested in human therapy to promote nerve recovery of function after different forms of neurodegeneration.<\/jats:p>","DOI":"10.3390\/cells8101183","type":"journal-article","created":{"date-parts":[[2019,9,30]],"date-time":"2019-09-30T13:16:41Z","timestamp":1569849401000},"page":"1183","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":24,"title":["An Agonist of the CXCR4 Receptor Strongly Promotes Regeneration of Degenerated Motor Axon Terminals"],"prefix":"10.3390","volume":"8","author":[{"given":"Samuele","family":"Negro","sequence":"first","affiliation":[{"name":"Department of Biomedical Sciences, University of Padua, 35131 Padua, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9350-1047","authenticated-orcid":false,"given":"Giulia","family":"Zanetti","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, University of Padua, 35131 Padua, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Mattarei","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical and Pharmacological Sciences, University of Padua, 35131 Padua, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alice","family":"Valentini","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical and Pharmacological Sciences, University of Padua, 35131 Padua, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aram","family":"Megighian","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, University of Padua, 35131 Padua, Italy"},{"name":"Padua Neuroscience Institute, 35131 Padua, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giulia","family":"Tombesi","sequence":"additional","affiliation":[{"name":"Department of Biology, University of Padua, 35131 Padua, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandro","family":"Zugno","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical and Pharmacological Sciences, University of Padua, 35131 Padua, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valentina","family":"Dianin","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical and Pharmacological Sciences, University of Padua, 35131 Padua, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4127-254X","authenticated-orcid":false,"given":"Marco","family":"Pirazzini","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, University of Padua, 35131 Padua, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5100-2573","authenticated-orcid":false,"given":"Silvia","family":"Fillo","sequence":"additional","affiliation":[{"name":"Center of Medical and Veterinary Research of the Ministry of Defence, 00184 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Florigio","family":"Lista","sequence":"additional","affiliation":[{"name":"Center of Medical and Veterinary Research of the Ministry of Defence, 00184 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michela","family":"Rigoni","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, University of Padua, 35131 Padua, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cesare","family":"Montecucco","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, University of Padua, 35131 Padua, Italy"},{"name":"CNR Institute of Neuroscience, 35131 Padua, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2019,9,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"389","DOI":"10.1146\/annurev.neuro.22.1.389","article-title":"Development of the vertebrate neuromuscular junction","volume":"22","author":"Sanes","year":"1999","journal-title":"Annu. 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