{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T23:10:25Z","timestamp":1782947425500,"version":"3.54.5"},"reference-count":70,"publisher":"MDPI AG","issue":"21","license":[{"start":{"date-parts":[[2024,10,28]],"date-time":"2024-10-28T00:00:00Z","timestamp":1730073600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Fondation J\u00e9r\u00f4me Lejeune","award":["GRT#2039"],"award-info":[{"award-number":["GRT#2039"]}]},{"name":"Fondation J\u00e9r\u00f4me Lejeune","award":["RV_TAR16SSONN_M"],"award-info":[{"award-number":["RV_TAR16SSONN_M"]}]},{"name":"Ministry of University and Research (MUR) Progetto Eccellenza (2023\u20132027) to the Department of Pharmacological and Biomolecular Sciences \u201cRodolfo Paoletti,\u201d Universit\u00e0 degli Studi di Milano","award":["GRT#2039"],"award-info":[{"award-number":["GRT#2039"]}]},{"name":"Ministry of University and Research (MUR) Progetto Eccellenza (2023\u20132027) to the Department of Pharmacological and Biomolecular Sciences \u201cRodolfo Paoletti,\u201d Universit\u00e0 degli Studi di Milano","award":["RV_TAR16SSONN_M"],"award-info":[{"award-number":["RV_TAR16SSONN_M"]}]},{"name":"Italian Ministry of Health with Ricerca Corrente and \u201c5xmille\u201d funds","award":["GRT#2039"],"award-info":[{"award-number":["GRT#2039"]}]},{"name":"Italian Ministry of Health with Ricerca Corrente and \u201c5xmille\u201d funds","award":["RV_TAR16SSONN_M"],"award-info":[{"award-number":["RV_TAR16SSONN_M"]}]},{"name":"\u201cFondi Tariffario\u201d","award":["GRT#2039"],"award-info":[{"award-number":["GRT#2039"]}]},{"name":"\u201cFondi Tariffario\u201d","award":["RV_TAR16SSONN_M"],"award-info":[{"award-number":["RV_TAR16SSONN_M"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Rett syndrome (RTT) is a severe neurodevelopmental disorder primarily caused by mutations in the methyl-CpG binding protein 2 (MECP2) gene. Despite advancements in research, no cure exists due to an incomplete understanding of the molecular effects of MeCP2 deficiency. Previous studies have identified impaired tropomyosin receptor kinase (Trk) neurotrophin (NTP) signaling and mitochondrial redox imbalances as key drivers of the pathology. Moreover, altered glycosphingolipid metabolism has been reported in RTT. GM1 ganglioside is a known regulator of the nervous system, and growing evidence indicates its importance in maintaining neuronal homeostasis via its oligosaccharide chain, coded as GM1-OS. GM1-OS directly interacts with the Trk receptors on the cell surface, triggering neurotrophic and neuroprotective pathways in neurons. In this study, we demonstrate that GM1-OS ameliorates RTT deficits in the Mecp2-null model. GM1-OS restored synaptogenesis and reduced mitochondrial oxidative stress of Mecp2-knock-out (ko) cortical neurons. When administered in vivo, GM1-OS mitigated RTT-like symptoms. Our findings indicate that GM1-OS effects were mediated by Trk receptor activation on the neuron\u2019s plasma membrane. Overall, our results highlight GM1-OS as a promising candidate for RTT treatment.<\/jats:p>","DOI":"10.3390\/ijms252111555","type":"journal-article","created":{"date-parts":[[2024,10,28]],"date-time":"2024-10-28T04:15:02Z","timestamp":1730088902000},"page":"11555","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["GM1 Oligosaccharide Ameliorates Rett Syndrome Phenotypes In Vitro and In Vivo via Trk Receptor Activation"],"prefix":"10.3390","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7034-9820","authenticated-orcid":false,"given":"Maria","family":"Fazzari","sequence":"first","affiliation":[{"name":"Department of Medical Biotechnology and Translational Medicine, Universit\u00e0 degli Studi di Milano, 20054 Segrate, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3099-3395","authenticated-orcid":false,"given":"Giulia","family":"Lunghi","sequence":"additional","affiliation":[{"name":"Department of Medical Biotechnology and Translational Medicine, Universit\u00e0 degli Studi di Milano, 20054 Segrate, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1486-550X","authenticated-orcid":false,"given":"Emma Veronica","family":"Carsana","sequence":"additional","affiliation":[{"name":"Department of Medical Biotechnology and Translational Medicine, Universit\u00e0 degli Studi di Milano, 20054 Segrate, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manuela","family":"Valsecchi","sequence":"additional","affiliation":[{"name":"Department of Medical Biotechnology and Translational Medicine, Universit\u00e0 degli Studi di Milano, 20054 Segrate, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eleonora","family":"Spiombi","sequence":"additional","affiliation":[{"name":"Department of Medical Biotechnology and Translational Medicine, Universit\u00e0 degli Studi di Milano, 20054 Segrate, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martina","family":"Breccia","sequence":"additional","affiliation":[{"name":"Department of Medical Biotechnology and Translational Medicine, Universit\u00e0 degli Studi di Milano, 20054 Segrate, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4393-7691","authenticated-orcid":false,"given":"Silvia Rosanna","family":"Casati","sequence":"additional","affiliation":[{"name":"Department of Medical Biotechnology and Translational Medicine, Universit\u00e0 degli Studi di Milano, 20054 Segrate, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6404-6321","authenticated-orcid":false,"given":"Silvia","family":"Pedretti","sequence":"additional","affiliation":[{"name":"Department of Pharmacological and Biomolecular Sciences \u201cRodolfo Paoletti\u201d, Universit\u00e0 degli Studi di Milano, 20133 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5000-3619","authenticated-orcid":false,"given":"Nico","family":"Mitro","sequence":"additional","affiliation":[{"name":"Department of Pharmacological and Biomolecular Sciences \u201cRodolfo Paoletti\u201d, Universit\u00e0 degli Studi di Milano, 20133 Milan, Italy"},{"name":"Department of Experimental Oncology, IEO, European Institute of Oncology IRCCS, 20139 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4194-4804","authenticated-orcid":false,"given":"Laura","family":"Mauri","sequence":"additional","affiliation":[{"name":"Department of Medical Biotechnology and Translational Medicine, Universit\u00e0 degli Studi di Milano, 20054 Segrate, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Grazia","family":"Ciampa","sequence":"additional","affiliation":[{"name":"Department of Medical Biotechnology and Translational Medicine, Universit\u00e0 degli Studi di Milano, 20054 Segrate, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8180-5908","authenticated-orcid":false,"given":"Sandro","family":"Sonnino","sequence":"additional","affiliation":[{"name":"Department of Medical Biotechnology and Translational Medicine, Universit\u00e0 degli Studi di Milano, 20054 Segrate, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0820-3155","authenticated-orcid":false,"given":"Nicoletta","family":"Landsberger","sequence":"additional","affiliation":[{"name":"Department of Medical Biotechnology and Translational Medicine, Universit\u00e0 degli Studi di Milano, 20054 Segrate, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0963-9789","authenticated-orcid":false,"given":"Angelisa","family":"Frasca","sequence":"additional","affiliation":[{"name":"Department of Medical Biotechnology and Translational Medicine, Universit\u00e0 degli Studi di Milano, 20054 Segrate, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7431-9207","authenticated-orcid":false,"given":"Elena","family":"Chiricozzi","sequence":"additional","affiliation":[{"name":"Department of Medical Biotechnology and Translational Medicine, Universit\u00e0 degli Studi di Milano, 20054 Segrate, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,10,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"422","DOI":"10.1016\/j.neuron.2007.10.001","article-title":"The story of Rett syndrome: From clinic to neurobiology","volume":"56","author":"Chahrour","year":"2007","journal-title":"Neuron"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1016\/j.neubiorev.2014.01.011","article-title":"Rett syndrome and the urge of novel approaches to study MeCP2 functions and mechanisms of action","volume":"46","author":"Bedogni","year":"2014","journal-title":"Neurosci. 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