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While neuronal degeneration has been largely described in experimental models and human patients, more subtle neuronal pathogenic defects remain still underexplored. In this work, we discovered that the axon guidance receptor Deleted in Colorectal Cancer (Dcc) is significantly dysregulated in the brain of\n                    <jats:italic>ids<\/jats:italic>\n                    mutant zebrafish since embryonic stages. In addition, thanks to the establishment of neuronal-enriched primary cell cultures, we identified defective proteasomal degradation as one of the main pathways underlying Dcc upregulation in\n                    <jats:italic>ids<\/jats:italic>\n                    mutant conditions. Furthermore,\n                    <jats:italic>ids<\/jats:italic>\n                    mutant fish-derived primary neurons displayed higher levels of polyubiquitinated proteins and P62, suggesting a wider defect in protein degradation. Finally, we show that\n                    <jats:italic>ids<\/jats:italic>\n                    mutant larvae display an atypical response to anxiety-inducing stimuli, hence mimicking one of the characteristic features of MPS II patients. Our study provides an additional relevant frame to MPS II pathogenesis, supporting the concept that multiple developmental defects concur with early childhood behavioural abnormalities.\n                  <\/jats:p>","DOI":"10.1038\/s41419-024-06661-2","type":"journal-article","created":{"date-parts":[[2024,4,16]],"date-time":"2024-04-16T15:01:35Z","timestamp":1713279695000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Mucopolysaccharidosis type II zebrafish model exhibits early impaired proteasomal-mediated degradation of the axon guidance receptor Dcc"],"prefix":"10.1038","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0009-0000-4505-0261","authenticated-orcid":false,"given":"Rosa","family":"Manzoli","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lorenzo","family":"Badenetti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7683-8107","authenticated-orcid":false,"given":"Matteo","family":"Bruzzone","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Carla","family":"Macario","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michela","family":"Rubin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marco","family":"Dal Maschio","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3252-0559","authenticated-orcid":false,"given":"Antonella","family":"Roveri","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3166-8102","authenticated-orcid":false,"given":"Enrico","family":"Moro","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,4,16]]},"reference":[{"key":"6661_CR1","doi-asserted-by":"publisher","first-page":"2515","DOI":"10.3390\/ijms21072515","volume":"21","author":"S Fecarotta","year":"2020","unstructured":"Fecarotta S, Tarallo A, Damiano C, Minopoli N, Parenti G. 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