{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T22:21:34Z","timestamp":1787178094345,"version":"build-2736575974"},"reference-count":41,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2025,8,7]],"date-time":"2025-08-07T00:00:00Z","timestamp":1754524800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Milano University","award":["PSR2022_DIP_003FAZZARI-SAVINO"],"award-info":[{"award-number":["PSR2022_DIP_003FAZZARI-SAVINO"]}]},{"name":"Milano University","award":["PSR2023_LUNGHI"],"award-info":[{"award-number":["PSR2023_LUNGHI"]}]},{"name":"Milano University","award":["INTLI25GLUNG_01"],"award-info":[{"award-number":["INTLI25GLUNG_01"]}]},{"name":"Mizutani Foundation for Glycoscience 2024","award":["PSR2022_DIP_003FAZZARI-SAVINO"],"award-info":[{"award-number":["PSR2022_DIP_003FAZZARI-SAVINO"]}]},{"name":"Mizutani Foundation for Glycoscience 2024","award":["PSR2023_LUNGHI"],"award-info":[{"award-number":["PSR2023_LUNGHI"]}]},{"name":"Mizutani Foundation for Glycoscience 2024","award":["INTLI25GLUNG_01"],"award-info":[{"award-number":["INTLI25GLUNG_01"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Neuroinflammation driven by microglial activation and \u03b1-synuclein (\u03b1Syn) aggregation is one of the central features driving Parkinson\u2019s disease (PD) pathogenesis. GM1 ganglioside\u2019s oligosaccharide moiety (OligoGM1) has shown neuroprotective potential in PD neuronal models, but its direct effects on inflammation remain poorly defined. This study investigated the ability of OligoGM1 to modulate microglial activation and \u03b1Syn handling in a human in vitro model. Human embryonic microglial (HMC3) cells were exposed to \u03b1Syn pre-formed fibrils (PFFs) in the presence or absence of OligoGM1. Microglial activation markers, intracellular \u03b1Syn accumulation, and cytokine release were assessed by immunofluorescence and ELISA. OligoGM1 had no effect on microglial morphology or cytokine release under basal conditions. Upon \u03b1Syn challenge, cells exhibited increased amounts of ionized calcium-binding adaptor molecule 1 (Iba1), triggered receptor expressed on myeloid cells 2 (TREM2), elevated \u03b1Syn accumulation, and secreted pro-inflammatory cytokines. OligoGM1 pre-treatment significantly reduced the number and area of Iba1(+) cells, the intracellular \u03b1Syn burden in TREM2(+) microglia, and the release of interleukin 6 (IL-6). OligoGM1 selectively attenuated \u03b1Syn-induced microglial activation and enhanced \u03b1Syn clearance without compromising basal immune function. These findings confirm and support the potential of OligoGM1 as a multitarget therapeutic candidate for PD that is capable of modulating glial reactivity and neuroinflammatory responses.<\/jats:p>","DOI":"10.3390\/ijms26157634","type":"journal-article","created":{"date-parts":[[2025,8,7]],"date-time":"2025-08-07T08:33:06Z","timestamp":1754555586000},"page":"7634","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["GM1 Oligosaccharide Modulates Microglial Activation and \u03b1-Synuclein Clearance in a Human In Vitro Model"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3099-3395","authenticated-orcid":false,"given":"Giulia","family":"Lunghi","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"}]},{"given":"Carola","family":"Pedroli","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\/0000-0002-4026-1067","authenticated-orcid":false,"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\/0000-0002-4194-4804","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":"Laura","family":"Rouvi\u00e8re","sequence":"additional","affiliation":[{"name":"Neuro-Sys, 410 Chemin D\u00e9partemental 60, 13120 Gardanne, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandre","family":"Henriques","sequence":"additional","affiliation":[{"name":"Neuro-Sys, 410 Chemin D\u00e9partemental 60, 13120 Gardanne, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4796-1592","authenticated-orcid":false,"given":"Noelle","family":"Callizot","sequence":"additional","affiliation":[{"name":"Neuro-Sys, 410 Chemin D\u00e9partemental 60, 13120 Gardanne, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benedetta","family":"Savino","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\/0000-0001-7034-9820","authenticated-orcid":false,"given":"Maria","family":"Fazzari","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":[[2025,8,7]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"384","DOI":"10.1212\/01.wnl.0000247740.47667.03","article-title":"Projected number of people with Parkinson disease in the most populous nations, 2005 through 2030","volume":"68","author":"Dorsey","year":"2007","journal-title":"Neurology"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Schneider, J.S. 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