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Novel and more effective therapies for UCD are needed. Studies in mice with constitutive activation of autophagy unravelled Beclin\u20101 as\n                    <jats:italic>druggable<\/jats:italic>\n                    candidate for therapy of hyperammonemia. Next, we investigated efficacy of cell\u2010penetrating autophagy\u2010inducing Tat\u2010Beclin\u20101 (TB\u20101) peptide for therapy of the two most common UCD, namely ornithine transcarbamylase (OTC) and argininosuccinate lyase (ASL) deficiencies. TB\u20101 reduced urinary orotic acid and improved survival under protein\u2010rich diet in\n                    <jats:italic>spf\u2010ash<\/jats:italic>\n                    mice, a model of OTC deficiency (proximal UCD). In\n                    <jats:italic>Asl<\/jats:italic>\n                    <jats:sup>\n                      <jats:italic>Neo\/Neo<\/jats:italic>\n                    <\/jats:sup>\n                    mice, a model of ASL deficiency (distal UCD), TB\u20101 increased ureagenesis, reduced argininosuccinate, and improved survival. Moreover, it alleviated hepatocellular injury and decreased both cytoplasmic and nuclear glycogen accumulation in\n                    <jats:italic>Asl<\/jats:italic>\n                    <jats:sup>\n                      <jats:italic>Neo\/Neo<\/jats:italic>\n                    <\/jats:sup>\n                    mice. In conclusion, Beclin\u20101\u2010dependent activation of autophagy improved biochemical and clinical phenotypes of proximal and distal defects of the urea cycle.\n                  <\/jats:p>","DOI":"10.15252\/emmm.202013158","type":"journal-article","created":{"date-parts":[[2020,12,28]],"date-time":"2020-12-28T08:36:48Z","timestamp":1609144608000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":31,"title":["Beclin\u20101\u2010mediated activation of autophagy improves proximal and distal urea cycle disorders"],"prefix":"10.1038","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7124-856X","authenticated-orcid":false,"given":"Leandro R","family":"Soria","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sonam","family":"Gurung","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giulia","family":"De Sabbata","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5450-8801","authenticated-orcid":false,"given":"Dany P","family":"Perocheau","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angela","family":"De Angelis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gemma","family":"Bruno","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena","family":"Polishchuk","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Debora","family":"Paris","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paola","family":"Cuomo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Motta","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Orford","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9025-3017","authenticated-orcid":false,"given":"Youssef","family":"Khalil","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simon","family":"Eaton","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philippa B","family":"Mills","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simon N","family":"Waddington","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5829-8589","authenticated-orcid":false,"given":"Carmine","family":"Settembre","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9628-0494","authenticated-orcid":false,"given":"Andr\u00e9s F","family":"Muro","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0582-540X","authenticated-orcid":false,"given":"Julien","family":"Baruteau","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6895-8819","authenticated-orcid":false,"given":"Nicola","family":"Brunetti\u2010Pierri","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2020,12,28]]},"reference":[{"key":"BFEMMM202013158_CR1","doi-asserted-by":"crossref","first-page":"985","DOI":"10.1016\/j.jhep.2019.01.026","volume":"70","author":"M Allaire","year":"2019","unstructured":"Allaire M, Rautou PE, Codogno P, Lotersztajn S (2019) Autophagy in liver diseases: time for translation? 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