{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,25]],"date-time":"2026-06-25T21:29:24Z","timestamp":1782422964847,"version":"3.54.5"},"reference-count":77,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2022,8,12]],"date-time":"2022-08-12T00:00:00Z","timestamp":1660262400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004434","name":"Universit\u00e0 degli Studi di Firenze","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004434","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100009888","name":"Regione Toscana","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100009888","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["febs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The FEBS Journal"],"published-print":{"date-parts":[[2023,1]]},"abstract":"<jats:p>\n                    Soluble oligomers arising from the aggregation of the amyloid beta peptide (A\u03b2) have been identified as the main pathogenic agents in Alzheimer's disease (AD). Prefibrillar oligomers of the 42\u2010residue form of A\u03b2 (A\u03b2\n                    <jats:sub>42<\/jats:sub>\n                    O) show membrane\u2010binding capacity and trigger the disruption of Ca\n                    <jats:sup>2+<\/jats:sup>\n                    homeostasis, a causative event in neuron degeneration. Since bioactive lipids have been recently proposed as potent protective agents against A\u03b2 toxicity, we investigated the involvement of sphingosine 1\u2010phosphate (S1P) signalling pathway in Ca\n                    <jats:sup>2+<\/jats:sup>\n                    homeostasis in living neurons exposed to A\u03b2\n                    <jats:sub>42<\/jats:sub>\n                    O. We show that both exogenous and endogenous S1P rescued neuronal Ca\n                    <jats:sup>2+<\/jats:sup>\n                    dyshomeostasis induced by toxic A\u03b2\n                    <jats:sub>42<\/jats:sub>\n                    O in primary rat cortical neurons and human neuroblastoma SH\u2010SY5Y cells. Further analysis revealed a strong neuroprotective effect of S1P\n                    <jats:sub>1<\/jats:sub>\n                    and S1P\n                    <jats:sub>4<\/jats:sub>\n                    receptors, and to a lower extent of S1P\n                    <jats:sub>3<\/jats:sub>\n                    and S1P\n                    <jats:sub>5<\/jats:sub>\n                    receptors, which activate the G\n                    <jats:sub>i<\/jats:sub>\n                    \u2010dependent signalling pathways, thus resulting in the endocytic internalization of the extrasynaptic GluN2B\u2010containing\n                    <jats:italic>N<\/jats:italic>\n                    \u2010methyl\u2010\n                    <jats:italic>D<\/jats:italic>\n                    \u2010aspartate receptors (NMDARs). Notably, the S1P beneficial effect can be sustained over time by sphingosine kinase\u20101 overexpression, thus counteracting the down\u2010regulation of the S1P signalling induced by A\u03b2\n                    <jats:sub>42<\/jats:sub>\n                    O. Our findings disclose underlying mechanisms of S1P neuronal protection against harmful A\u03b2\n                    <jats:sub>42<\/jats:sub>\n                    O, suggesting that S1P and its signalling axis can be considered promising targets for therapeutic approaches for AD.\n                  <\/jats:p>","DOI":"10.1111\/febs.16579","type":"journal-article","created":{"date-parts":[[2022,7,19]],"date-time":"2022-07-19T03:55:27Z","timestamp":1658202927000},"page":"112-133","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Sphingosine 1\u2010phosphate attenuates neuronal dysfunction induced by amyloid\u2010\u03b2 oligomers through endocytic internalization of\n                    <scp>NMDA<\/scp>\n                    receptors"],"prefix":"10.1111","volume":"290","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1067-6288","authenticated-orcid":false,"given":"Alessandra","family":"Bigi","sequence":"first","affiliation":[{"name":"Department of Experimental and Clinical Biomedical Sciences University of Florence  Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9856-6843","authenticated-orcid":false,"given":"Roberta","family":"Cascella","sequence":"additional","affiliation":[{"name":"Department of Experimental and Clinical Biomedical Sciences University of Florence  Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2831-7811","authenticated-orcid":false,"given":"Giulia","family":"Fani","sequence":"additional","affiliation":[{"name":"Department of Experimental and Clinical Biomedical Sciences University of Florence  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