{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T13:54:51Z","timestamp":1787579691952,"version":"build-2736575974"},"reference-count":53,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2023,1,4]],"date-time":"2023-01-04T00:00:00Z","timestamp":1672790400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft (DFG)","doi-asserted-by":"publisher","award":["HO 2402\/18-1"],"award-info":[{"award-number":["HO 2402\/18-1"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Karlheinz-Hartmann-Stiftung (Hannover, Germany)","award":["HO 2402\/18-1"],"award-info":[{"award-number":["HO 2402\/18-1"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Multiple system atrophy of the parkinsonian type (MSA-P) is a rare, fatal neurodegenerative disease with sporadic onset. It is still unknown if MSA-P is a primary oligodendropathy or caused by neuronal pathophysiology leading to severe, \u03b1-synuclein-associated neurodegeneration, mainly in the striatum. In this study, we generated and differentiated induced pluripotent stem cells (iPSCs) from patients with the clinical diagnosis of probable MSA-P (n = 3) and from three matched healthy controls into GABAergic striatal medium spiny neurons (MSNs). We found a significantly elevated release and neuronal distribution for \u03b1-synuclein, as well as hypoexcitability in the MSNs derived from the MSA-P patients compared to the healthy controls. These data suggest that the striatal hypoexcitable neurons of MSA-P patients contribute to a pathological \u03b1-synuclein burden which is likely to spread to neighboring cells and projection targets, facilitating disease progression.<\/jats:p>","DOI":"10.3390\/cells12020223","type":"journal-article","created":{"date-parts":[[2023,1,5]],"date-time":"2023-01-05T01:33:30Z","timestamp":1672882410000},"page":"223","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["iPSC-Derived Striatal Medium Spiny Neurons from Patients with Multiple System Atrophy Show Hypoexcitability and Elevated \u03b1-Synuclein Release"],"prefix":"10.3390","volume":"12","author":[{"given":"Lisa M.","family":"Henkel","sequence":"first","affiliation":[{"name":"Department of Neurology, Hannover Medical School, Carl-Neuberg-Str. 1, 30625 Hannover, Germany"},{"name":"Center for Systems Neuroscience, B\u00fcnteweg 2, 30559 Hannover, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0387-3184","authenticated-orcid":false,"given":"Svenja","family":"Kankowski","sequence":"additional","affiliation":[{"name":"Institute of Neuroanatomy and Cell Biology, Hannover Medical School, 30625 Hanover, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thiemo M.","family":"Moellenkamp","sequence":"additional","affiliation":[{"name":"Department of Neurology, Hannover Medical School, Carl-Neuberg-Str. 1, 30625 Hannover, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nadine J.","family":"Smandzich","sequence":"additional","affiliation":[{"name":"Department of Neurology, Hannover Medical School, Carl-Neuberg-Str. 1, 30625 Hannover, Germany"},{"name":"Center for Systems Neuroscience, B\u00fcnteweg 2, 30559 Hannover, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sigrid","family":"Schwarz","sequence":"additional","affiliation":[{"name":"Curiositas-ad-sanum Studien und Beratungs GmbH, Krankenhausstr. 3, 83527 Haag in Oberbayern, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6478-026X","authenticated-orcid":false,"given":"Alessio","family":"Di Fonzo","sequence":"additional","affiliation":[{"name":"Foundation IRCCS Ca\u2019 Granda Hospital Maggiore Policlinico, Unit\u00e0 di Neurologia, 20122 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gudrun","family":"G\u00f6hring","sequence":"additional","affiliation":[{"name":"Department of Human Genetics, Hannover Medical School, Carl-Neuberg-Str. 1, 30625 Hannover, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7587-6187","authenticated-orcid":false,"given":"G\u00fcnter","family":"H\u00f6glinger","sequence":"additional","affiliation":[{"name":"Department of Neurology, Hannover Medical School, Carl-Neuberg-Str. 1, 30625 Hannover, Germany"},{"name":"Center for Systems Neuroscience, B\u00fcnteweg 2, 30559 Hannover, Germany"},{"name":"Department of Neurology, University Hospital of Munich, Marchioninistr. 15, 81377 Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Florian","family":"Wegner","sequence":"additional","affiliation":[{"name":"Department of Neurology, Hannover Medical School, Carl-Neuberg-Str. 1, 30625 Hannover, Germany"},{"name":"Center for Systems Neuroscience, B\u00fcnteweg 2, 30559 Hannover, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,1,4]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"670","DOI":"10.1212\/01.wnl.0000324625.00404.15","article-title":"Second consensus statement on the diagnosis of multiple system atrophy","volume":"71","author":"Gilman","year":"2008","journal-title":"Neurology"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1131","DOI":"10.1002\/mds.29005","article-title":"The Movement Disorder Society Criteria for the Diagnosis of Multiple System Atrophy","volume":"37","author":"Wenning","year":"2022","journal-title":"Mov. 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