{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T06:41:49Z","timestamp":1792219309254,"version":"4.4.0"},"reference-count":29,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T00:00:00Z","timestamp":1792108800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T00:00:00Z","timestamp":1792108800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100021856","name":"Ministero dell'Universit\u00e0 e della Ricerca","doi-asserted-by":"publisher","award":["D33C22001340002"],"award-info":[{"award-number":["D33C22001340002"]}],"id":[{"id":"10.13039\/501100021856","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100021856","name":"Ministero dell'Universit\u00e0 e della Ricerca","doi-asserted-by":"publisher","award":["F63C22000640002"],"award-info":[{"award-number":["F63C22000640002"]}],"id":[{"id":"10.13039\/501100021856","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["movementdisorders.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Movement Disorders"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Progressive supranuclear palsy (PSP) is a devastating 4\u2010repeat tauopathy with no approved disease\u2010modifying treatments. Recent evidence showed increased transforming growth factor\u2010\u03b2 (TGF\u2010\u03b2) levels in PSP patient\u2010derived ventral midbrain organoids (vMOs) and serum neuronally derived exosomes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>This study investigated whether TGF\u2010\u03b2 pharmacological inhibition could mitigate PSP pathology in vMOs.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Ninety\u2010six vMOs were generated from induced pluripotent stem cells from two PSP\u2010Richardson's syndrome patients and two healthy control donors (HCs). From day 60 to day 90, PSP organoids were (1) exposed to TGF\u2010\u03b2 receptor I inhibitor (SB431542); (2) exposed to recombinant TGF\u2010\u03b21, TGF\u2010\u03b22, and TGF\u2010\u03b23; or (3) untreated. At day 90, several tau species were assessed by immunoblotting; neurodegeneration was evaluated through TUNEL assay and immunofluorescence (tyrosine hydroxylase [TH], neurofilament light chain [NfL]); astrocytic activation\u00a0(glial fibrillary acidic protein [GFAP]) marker was evaluated by immunofluorescence, and histopathological hallmarks were evaluated by immunohistochemistry. An HC\u2010derived organoid subgroup was exposed to the treatment conditions to assess potential toxicity.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>At day 90, untreated PSP\u2010derived vMOs exhibited increased phosphorylated tau levels (Ser396, Thr181, Ser202\/Ser205 [AT8]) compared with HC\u2010derived vMOs, dopaminergic neuron loss (reduced TH, increased NfL), and astrocytic reactivity (increased GFAP), along with PSP characteristic tau deposition. Tau hyperphosphorylation, neurodegeneration, and astrocytic reactivity were all markedly reduced in PSP\u2010derived vMOs treated with TGF\u2010\u03b2 receptor I inhibitor. Conversely, exposure to TGF\u2010\u03b2 exacerbated these features. No toxic effects were observed in HC vMOs exposed to treatment conditions.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      Pharmacological inhibition of TGF\u2010\u03b2 signaling prevented key PSP molecular alterations in patient\u2010derived organoids. These findings support further research and pave the way for future investigation of TGF\u2010\u03b2\u2013targeting strategies in clinical trials in patients with PSP. \u00a9 2026 The Author(s).\n                      <jats:italic>Movement Disorders<\/jats:italic>\n                      published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/mds.70574","type":"journal-article","created":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T06:06:02Z","timestamp":1792217162000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["<scp>TGF<\/scp>\n                    \u2010\u03b2 Inhibition Attenuates Tau Accumulation and Neurodegeneration in Progressive Supranuclear Palsy Patient\u2010Derived Organoids"],"prefix":"10.1002","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7439-3973","authenticated-orcid":false,"given":"Mariagrazia","family":"Talarico","sequence":"first","affiliation":[{"name":"Laboratory of Stem Cells, Research Centre for Biochemistry and Advanced Molecular Biology, Department of Experimental and Clinical Medicine University \u201cMagna Graecia\u201d  Catanzaro Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2071-2083","authenticated-orcid":false,"given":"Andrea","family":"Quattrone","sequence":"additional","affiliation":[{"name":"Department of Medical and Surgical Sciences Institute of Neurology, University \u201cMagna Graecia\u201d  Catanzaro Italy"},{"name":"Neuroscience Research Centre University \u201cMagna Graecia\u201d  Catanzaro Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-8585-2144","authenticated-orcid":false,"given":"Giorgia Lucia","family":"Benedetto","sequence":"additional","affiliation":[{"name":"Laboratory of Stem Cells, Research Centre for Biochemistry and Advanced Molecular Biology, Department of Experimental and Clinical Medicine University \u201cMagna Graecia\u201d  Catanzaro Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-2571-2879","authenticated-orcid":false,"given":"Raffaele","family":"Covello","sequence":"additional","affiliation":[{"name":"Laboratory of Stem Cells, Research Centre for Biochemistry and Advanced Molecular Biology, Department of Experimental and Clinical Medicine University \u201cMagna Graecia\u201d  Catanzaro Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6260-6310","authenticated-orcid":false,"given":"Maurizio","family":"Martini","sequence":"additional","affiliation":[{"name":"Section of Pathology, Department of Human Pathology of Adult and Developmental Age \u201cGaetano Barresi\u201d University of Messina  Messina Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3478-9217","authenticated-orcid":false,"given":"Valeria","family":"Zuccal\u00e0","sequence":"additional","affiliation":[{"name":"Section of Pathology, Department of Human Pathology of Adult and Developmental Age \u201cGaetano Barresi\u201d University of Messina  Messina Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6313-1866","authenticated-orcid":false,"given":"Giovanni","family":"Cuda","sequence":"additional","affiliation":[{"name":"Laboratory of Stem Cells, Research Centre for Biochemistry and Advanced Molecular Biology, Department of Experimental and Clinical Medicine University \u201cMagna Graecia\u201d  Catanzaro Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8145-3623","authenticated-orcid":false,"given":"Elvira Immacolata","family":"Parrotta","sequence":"additional","affiliation":[{"name":"Laboratory of Stem Cells, Department of Medical and Surgical Sciences University \u201cMagna Graecia\u201d  Catanzaro Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2001-957X","authenticated-orcid":false,"given":"Aldo","family":"Quattrone","sequence":"additional","affiliation":[{"name":"Neuroscience Research Centre University \u201cMagna Graecia\u201d  Catanzaro Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,10,16]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-020-02158-2"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-021-01455-x"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(20)30489-0"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1080\/13543784.2022.2087179"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/mds.70049"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.27172"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-024-52173-0"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/mds.30222"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41392-024-01764-w"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1186\/1750-1326-2-12"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-002-0587-8"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1002\/mds.26987"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1111\/jcmm.14426"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1002\/cpz1.555"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1260419"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.abh2169"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.2174\/1389203719666171129094937"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0116549"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.3390\/biomedicines10051206"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1097\/00001756-199301000-00018"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/s0197-4580(98)00089-x"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1006\/neur.1995.0051"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.26962"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1002\/mds.25815"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1002\/trc2.70098"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13195-025-01775-x"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ekir.2017.03.011"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0090353"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awv222"}],"container-title":["Movement Disorders"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/movementdisorders.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/mds.70574","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/movementdisorders.onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/mds.70574","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/movementdisorders.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/mds.70574","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T06:06:04Z","timestamp":1792217164000},"score":1,"resource":{"primary":{"URL":"https:\/\/movementdisorders.onlinelibrary.wiley.com\/doi\/10.1002\/mds.70574"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,10,16]]},"references-count":29,"alternative-id":["10.1002\/mds.70574"],"URL":"https:\/\/doi.org\/10.1002\/mds.70574","archive":["Portico"],"relation":{},"ISSN":["0885-3185","1531-8257"],"issn-type":[{"value":"0885-3185","type":"print"},{"value":"1531-8257","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,10,16]]},"assertion":[{"value":"2026-03-26","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-09-24","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-10-16","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"mds.70574"}}