{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T11:50:32Z","timestamp":1790769032307,"version":"4.1.0"},"reference-count":36,"publisher":"Oxford University Press (OUP)","issue":"13","license":[{"start":{"date-parts":[[2021,2,18]],"date-time":"2021-02-18T00:00:00Z","timestamp":1613606400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"name":"Telethon","award":["GGP13053"],"award-info":[{"award-number":["GGP13053"]}]},{"name":"Programmi di Ricerca Scientifica di Rilevante Interesse Nazionale","award":["20128XWKTX"],"award-info":[{"award-number":["20128XWKTX"]}]},{"name":"ModelPolyQ","award":["JPCOFUND-643417"],"award-info":[{"award-number":["JPCOFUND-643417"]}]},{"name":"CircProt","award":["JPCOFUND-643417"],"award-info":[{"award-number":["JPCOFUND-643417"]}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["DFG-SFB877-A3"],"award-info":[{"award-number":["DFG-SFB877-A3"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,6,17]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Synaptic dysfunction and cognitive decline in Huntington\u2019s disease (HD) involve hyperactive A disintegrin and metalloproteinase domain-containing protein 10 (ADAM10). To identify the molecular mechanisms through which ADAM10 is associated with synaptic dysfunction in HD, we performed an immunoaffinity purification\u2013mass spectrometry (IP\u2013MS) study of endogenous ADAM10 in the brains of wild-type and HD mice. We found that proteins implicated in synapse organization, synaptic plasticity, and vesicle and organelles trafficking interact with ADAM10, suggesting that it may act as hub protein at the excitatory synapse. Importantly, the ADAM10 interactome is enriched in presynaptic proteins and ADAM10 co-immunoprecipitates with piccolo (PCLO), a key player in the recycling and maintenance of synaptic vesicles. In contrast, reduced ADAM10\/PCLO immunoprecipitation occurs in the HD brain, with decreased density of synaptic vesicles in the reserve and docked pools at the HD presynaptic terminal. Conditional heterozygous deletion of ADAM10 in the forebrain of HD mice reduces active ADAM10 to wild-type level and normalizes ADAM10\/PCLO complex formation and synaptic vesicle density and distribution. The results indicate that presynaptic ADAM10 and PCLO are a relevant component of HD pathogenesis.<\/jats:p>","DOI":"10.1093\/hmg\/ddab047","type":"journal-article","created":{"date-parts":[[2021,2,5]],"date-time":"2021-02-05T20:29:39Z","timestamp":1612556979000},"page":"1175-1187","source":"Crossref","is-referenced-by-count":23,"title":["ADAM10 hyperactivation acts on piccolo to deplete synaptic vesicle stores in Huntington\u2019s disease"],"prefix":"10.1093","volume":"30","author":[{"given":"Flora","family":"Cozzolino","sequence":"first","affiliation":[{"name":"Department of Chemical Sciences, University of Naples \u201cFederico II\u201d, Naples 80126, Italy"},{"name":"CEINGE Advanced Biotechnologies, Naples 80131, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena","family":"Vezzoli","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences for Health, University of Milan, Milan 20133, 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