{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T15:02:30Z","timestamp":1787065350214,"version":"build-2736575974"},"reference-count":65,"publisher":"Springer Science and Business Media LLC","issue":"5","license":[{"start":{"date-parts":[[2025,2,15]],"date-time":"2025-02-15T00:00:00Z","timestamp":1739577600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2025,2,15]],"date-time":"2025-02-15T00:00:00Z","timestamp":1739577600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"University of Innsbruck and Medical University of Innsbruck"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["J Neural Transm"],"published-print":{"date-parts":[[2026,5]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Multiple system atrophy (MSA) is a fatal neurodegenerative disorder characterized by abnormal accumulation of \u03b1-synuclein, progressive neuronal loss, motor impairment and widespread pathological changes, which include significant involvement of the cerebellum. To understand the early molecular mechanisms that might underlie \u03b1-synuclein-triggered MSA cerebellar pathology, we performed RNA sequencing (RNA-Seq) of cerebellar samples from a well-established model of MSA. RNA-Seq and differential gene expression analysis was conducted in the PLP-\u03b1Syn model of MSA. Cerebellum from two and 12-month-old MSA and wildtype mice were used. Gene ontology (GO) and KEGG enrichment analyses of the differentially expressed genes (DEGs) were performed to explore processes involved in MSA-like disease progression. The overlap between transcriptional changes in MSA and those associated with aging was also evaluated. RNA-Seq analysis demonstrated significant transcriptional dysregulation in cerebellum from MSA mice, even at early stages. GO and KEGG analyses of DEGs point to a potential role of synaptic dysfunction, cellular signaling dysregulation and inflammation in the cerebellar pathology of MSA mice. In addition, those changes exacerbate with disease progression. Additionally, our analysis of aging in both control and PLP-\u03b1Syn mice showed that age-related transcriptional changes in mid-aged controls seem to be present in young MSA mice. Thus, MSA-like pathology might lead to an acceleration of aging-related mechanisms. Our findings demonstrate significant cerebellar transcriptional dysregulation triggered by oligodendroglial \u03b1-synucleinopathy in PLP-\u03b1Syn mice, revealing pathways that might be critical for the early cerebellar pathology of MSA, and that may serve as potential molecular targets for therapeutic interventions in this devastating disorder.<\/jats:p>","DOI":"10.1007\/s00702-025-02892-5","type":"journal-article","created":{"date-parts":[[2025,2,15]],"date-time":"2025-02-15T07:06:12Z","timestamp":1739603172000},"page":"795-808","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Transcriptional dysregulation in the cerebellum triggered by oligodendroglial \u03b1-synucleinopathy: insights from a transgenic mouse into the early disease mechanisms of MSA"],"prefix":"10.1007","volume":"133","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2231-2681","authenticated-orcid":false,"given":"Antonio","family":"Heras-Garvin","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lisa","family":"Fellner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roberta","family":"Granata","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gregor K.","family":"Wenning","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nadia","family":"Stefanova","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,2,15]]},"reference":[{"issue":"1","key":"2892_CR1","doi-asserted-by":"publisher","first-page":"4","DOI":"10.1111\/j.1365-2990.2011.01234.x","volume":"38","author":"Z Ahmed","year":"2012","unstructured":"Ahmed Z, Asi YT, Sailer A, Lees AJ, Houlden H, Revesz T, Holton JL (2012) The neuropathology, pathophysiology and genetics of multiple system atrophy. Neuropathol Appl Neurobiol 38(1):4\u201324. https:\/\/doi.org\/10.1111\/j.1365-2990.2011.01234.x","journal-title":"Neuropathol Appl Neurobiol"},{"issue":"34","key":"2892_CR2","doi-asserted-by":"publisher","first-page":"9593","DOI":"10.1073\/pnas.1609291113","volume":"113","author":"F Bassil","year":"2016","unstructured":"Bassil F, Fernagut PO, Bezard E, Pruvost A, Leste-Lasserre T, Hoang QQ, Meissner WG (2016) Reducing C-terminal truncation mitigates synucleinopathy and neurodegeneration in a transgenic model of multiple system atrophy. Proc Natl Acad Sci U S A 113(34):9593\u20139598. https:\/\/doi.org\/10.1073\/pnas.1609291113","journal-title":"Proc Natl Acad Sci U S A"},{"key":"2892_CR3","doi-asserted-by":"publisher","first-page":"75","DOI":"10.1186\/s40478-015-0254-7","volume":"3","author":"ME Bernis","year":"2015","unstructured":"Bernis ME, Babila JT, Breid S, Wusten KA, Wullner U, Tamguney G (2015) Prion-like propagation of human brain-derived alpha-synuclein in transgenic mice expressing human wild-type alpha-synuclein. Acta Neuropathol Commun 3:75. https:\/\/doi.org\/10.1186\/s40478-015-0254-7","journal-title":"Acta Neuropathol Commun"},{"issue":"3","key":"2892_CR4","doi-asserted-by":"publisher","first-page":"331","DOI":"10.3233\/JPD-130203","volume":"3","author":"JM Bleasel","year":"2013","unstructured":"Bleasel JM, Hsiao JH, Halliday GM, Kim WS (2013) Increased expression of ABCA8 in multiple system atrophy brain is associated with changes in pathogenic proteins. J Parkinsons Dis 3(3):331\u2013339. https:\/\/doi.org\/10.3233\/JPD-130203","journal-title":"J Parkinsons Dis"},{"issue":"3","key":"2892_CR5","doi-asserted-by":"publisher","first-page":"347","DOI":"10.1002\/mds.25336","volume":"28","author":"M Boudes","year":"2013","unstructured":"Boudes M, Uvin P, Pinto S, Voets T, Fowler CJ, Wenning GK, Stefanova N (2013) Bladder dysfunction in a transgenic mouse model of multiple system atrophy. Mov Disord 28(3):347\u2013355. https:\/\/doi.org\/10.1002\/mds.25336","journal-title":"Mov Disord"},{"key":"2892_CR6","doi-asserted-by":"publisher","first-page":"14","DOI":"10.1186\/s40673-014-0014-7","volume":"1","author":"L Ciolli","year":"2014","unstructured":"Ciolli L, Krismer F, Nicoletti F, Wenning GK (2014) An update on the cerebellar subtype of multiple system atrophy. Cerebellum Ataxias 1:14. https:\/\/doi.org\/10.1186\/s40673-014-0014-7","journal-title":"Cerebellum Ataxias"},{"issue":"1","key":"2892_CR7","doi-asserted-by":"publisher","first-page":"11","DOI":"10.1186\/s40478-023-01710-x","volume":"12","author":"NJ Corbin-Stein","year":"2024","unstructured":"Corbin-Stein NJ, Childers GM, Webster JM, Zane A, Yang YT, Mudium N, Harms AS (2024) IFNgamma drives neuroinflammation, demyelination, and neurodegeneration in a mouse model of multiple system atrophy. Acta Neuropathol Commun 12(1):11. https:\/\/doi.org\/10.1186\/s40478-023-01710-x","journal-title":"Acta Neuropathol Commun"},{"key":"2892_CR8","doi-asserted-by":"publisher","unstructured":"D\u2019Sa K, Choi ML, Wagen AZ, Set\u00f3-Salvia N, Kopach O, Evans JR, Ryten M (2024) Alpha-synuclein aggregates trigger anti-viral immune pathways and RNA editing in human astrocytes. 2024.2002.2026.582055. https:\/\/doi.org\/10.1101\/2024.02.26.582055%JbioRxiv","DOI":"10.1101\/2024.02.26.582055%JbioRxiv"},{"issue":"1","key":"2892_CR9","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1093\/bioinformatics\/bts635","volume":"29","author":"A Dobin","year":"2013","unstructured":"Dobin A, Davis CA, Schlesinger F, Drenkow J, Zaleski C, Jha S, Gingeras TR (2013) STAR: ultrafast universal RNA-seq aligner. Bioinformatics 29(1):15\u201321. https:\/\/doi.org\/10.1093\/bioinformatics\/bts635","journal-title":"Bioinformatics"},{"issue":"3","key":"2892_CR10","doi-asserted-by":"publisher","first-page":"249","DOI":"10.1056\/NEJMra1311488","volume":"372","author":"A Fanciulli","year":"2015","unstructured":"Fanciulli A, Wenning GK (2015) Multiple-system atrophy. N Engl J Med 372(3):249\u2013263. https:\/\/doi.org\/10.1056\/NEJMra1311488","journal-title":"N Engl J Med"},{"issue":"1","key":"2892_CR11","doi-asserted-by":"publisher","first-page":"87","DOI":"10.1007\/s00401-021-02316-0","volume":"142","author":"N Ferreira","year":"2021","unstructured":"Ferreira N, Gram H, Sorrentino ZA, Gregersen E, Schmidt SI, Reimer L, Jensen PH (2021) Multiple system atrophy-associated oligodendroglial protein p25alpha stimulates formation of novel alpha-synuclein strain with enhanced neurodegenerative potential. Acta Neuropathol 142(1):87\u2013115. https:\/\/doi.org\/10.1007\/s00401-021-02316-0","journal-title":"Acta Neuropathol"},{"issue":"1","key":"2892_CR12","doi-asserted-by":"publisher","first-page":"359","DOI":"10.1038\/s41392-023-01588-0","volume":"8","author":"C Gao","year":"2023","unstructured":"Gao C, Jiang J, Tan Y, Chen S (2023) Microglia in neurodegenerative diseases: mechanism and potential therapeutic targets. Signal Transduct Target Ther 8(1):359. https:\/\/doi.org\/10.1038\/s41392-023-01588-0","journal-title":"Signal Transduct Target Ther"},{"issue":"2","key":"2892_CR13","doi-asserted-by":"publisher","first-page":"338","DOI":"10.1002\/mds.29291","volume":"38","author":"ME Garcia-Segura","year":"2023","unstructured":"Garcia-Segura ME, Perez-Rodriguez D, Chambers D, Jaunmuktane Z, Proukakis C (2023) Somatic SNCA Copy Number variants in multiple system atrophy are related to Pathology and inclusions. Mov Disord 38(2):338\u2013342. https:\/\/doi.org\/10.1002\/mds.29291","journal-title":"Mov Disord"},{"key":"2892_CR14","doi-asserted-by":"publisher","first-page":"104846","DOI":"10.1016\/j.yexmp.2022.104846","volume":"129","author":"A Goyal","year":"2023","unstructured":"Goyal A, Agrawal A, Verma A, Dubey N (2023) The PI3K-AKT pathway: a plausible therapeutic target in Parkinson\u2019s disease. Exp Mol Pathol 129:104846. https:\/\/doi.org\/10.1016\/j.yexmp.2022.104846","journal-title":"Exp Mol Pathol"},{"key":"2892_CR15","doi-asserted-by":"publisher","unstructured":"Heras-Garvin A, Stefanova N (2020) From synaptic protein to prion: the long and controversial journey of \u03b1-Synuclein. Front Synaptic Neurosci 12(42). https:\/\/doi.org\/10.3389\/fnsyn.2020.584536","DOI":"10.3389\/fnsyn.2020.584536"},{"issue":"1","key":"2892_CR16","doi-asserted-by":"publisher","first-page":"19","DOI":"10.1186\/s13024-020-00368-6","volume":"15","author":"BA Hijaz","year":"2020","unstructured":"Hijaz BA, Volpicelli-Daley LA (2020) Initiation and propagation of alpha-synuclein aggregation in the nervous system. Mol Neurodegener 15(1):19. https:\/\/doi.org\/10.1186\/s13024-020-00368-6","journal-title":"Mol Neurodegener"},{"issue":"1","key":"2892_CR17","doi-asserted-by":"publisher","first-page":"73","DOI":"10.1007\/s00401-020-02163-5","volume":"142","author":"SAM Holec","year":"2021","unstructured":"Holec SAM, Woerman AL (2021) Evidence of distinct alpha-synuclein strains underlying disease heterogeneity. Acta Neuropathol 142(1):73\u201386. https:\/\/doi.org\/10.1007\/s00401-020-02163-5","journal-title":"Acta Neuropathol"},{"issue":"5","key":"2892_CR18","doi-asserted-by":"publisher","first-page":"727","DOI":"10.1002\/glia.23129","volume":"65","author":"T Ishimoto","year":"2017","unstructured":"Ishimoto T, Ninomiya K, Inoue R, Koike M, Uchiyama Y, Mori H (2017) Mice lacking BCAS1, a novel myelin-associated protein, display hypomyelination, schizophrenia-like abnormal behaviors, and upregulation of inflammatory genes in the brain. Glia 65(5):727\u2013739. https:\/\/doi.org\/10.1002\/glia.23129","journal-title":"Glia"},{"issue":"6","key":"2892_CR19","doi-asserted-by":"publisher","first-page":"583","DOI":"10.1093\/embo-reports\/kvf109","volume":"3","author":"PJ Kahle","year":"2002","unstructured":"Kahle PJ, Neumann M, Ozmen L, Muller V, Jacobsen H, Spooren W, Haass C (2002) Hyperphosphorylation and insolubility of alpha-synuclein in transgenic mouse oligodendrocytes. EMBO Rep 3(6):583\u2013588. https:\/\/doi.org\/10.1093\/embo-reports\/kvf109","journal-title":"EMBO Rep"},{"issue":"4","key":"2892_CR20","doi-asserted-by":"publisher","first-page":"396","DOI":"10.1016\/j.bbadis.2009.12.009","volume":"1802","author":"EK Kim","year":"2010","unstructured":"Kim EK, Choi EJ (2010) Pathological roles of MAPK signaling pathways in human diseases. Biochim Biophys Acta 1802(4):396\u2013405. https:\/\/doi.org\/10.1016\/j.bbadis.2009.12.009","journal-title":"Biochim Biophys Acta"},{"issue":"3","key":"2892_CR21","doi-asserted-by":"publisher","first-page":"401","DOI":"10.1042\/BJ20121764","volume":"452","author":"WS Kim","year":"2013","unstructured":"Kim WS, Hsiao JH, Bhatia S, Glaros EN, Don AS, Tsuruoka S, Halliday GM (2013) ABCA8 stimulates sphingomyelin production in oligodendrocytes. Biochem J 452(3):401\u2013410. https:\/\/doi.org\/10.1042\/BJ20121764","journal-title":"Biochem J"},{"key":"2892_CR22","doi-asserted-by":"publisher","first-page":"106551","DOI":"10.1016\/j.nbd.2024.106551","volume":"198","author":"T Kon","year":"2024","unstructured":"Kon T, Forrest SL, Lee S, Li J, Chasiotis H, Nassir N, Kovacs GG (2024) SNCA and TPPP transcripts increase in oligodendroglial cytoplasmic inclusions in multiple system atrophy. Neurobiol Dis 198:106551. https:\/\/doi.org\/10.1016\/j.nbd.2024.106551","journal-title":"Neurobiol Dis"},{"issue":"5","key":"2892_CR23","doi-asserted-by":"publisher","first-page":"e64625","DOI":"10.1371\/journal.pone.0064625","volume":"8","author":"F Krismer","year":"2013","unstructured":"Krismer F, Wenning GK, Li Y, Poewe W, Stefanova N (2013) Intact olfaction in a mouse model of multiple system atrophy. PLoS ONE 8(5):e64625. https:\/\/doi.org\/10.1371\/journal.pone.0064625","journal-title":"PLoS ONE"},{"issue":"4","key":"2892_CR24","doi-asserted-by":"publisher","first-page":"fcac165","DOI":"10.1093\/braincomms\/fcac165","volume":"4","author":"AS Kulkarni","year":"2022","unstructured":"Kulkarni AS, Burns MR, Brundin P, Wesson DW (2022) Linking alpha-synuclein-induced synaptopathy and neural network dysfunction in early Parkinson\u2019s disease. Brain Commun 4(4):fcac165. https:\/\/doi.org\/10.1093\/braincomms\/fcac165","journal-title":"Brain Commun"},{"key":"2892_CR25","doi-asserted-by":"publisher","first-page":"531","DOI":"10.1016\/j.expneurol.2013.02.002","volume":"247","author":"D Kuzdas","year":"2013","unstructured":"Kuzdas D, Stemberger S, Gaburro S, Stefanova N, Singewald N, Wenning GK (2013) Oligodendroglial alpha-synucleinopathy and MSA-like cardiovascular autonomic failure: experimental evidence. Exp Neurol 247:531\u2013536. https:\/\/doi.org\/10.1016\/j.expneurol.2013.02.002","journal-title":"Exp Neurol"},{"issue":"8","key":"2892_CR26","doi-asserted-by":"publisher","first-page":"e47","DOI":"10.1093\/nar\/gkz114","volume":"47","author":"Y Liao","year":"2019","unstructured":"Liao Y, Smyth GK, Shi W (2019) The R package rsubread is easier, faster, cheaper and better for alignment and quantification of RNA sequencing reads. Nucleic Acids Res 47(8):e47. https:\/\/doi.org\/10.1093\/nar\/gkz114","journal-title":"Nucleic Acids Res"},{"issue":"1","key":"2892_CR27","doi-asserted-by":"publisher","first-page":"100147","DOI":"10.1016\/j.jlr.2021.100147","volume":"63","author":"Y Liu","year":"2022","unstructured":"Liu Y, Castano D, Girolamo F, Trigueros-Motos L, Bae HG, Neo SP, Singaraja RR (2022) Loss of ABCA8B decreases myelination by reducing oligodendrocyte precursor cells in mice. J Lipid Res 63(1):100147. https:\/\/doi.org\/10.1016\/j.jlr.2021.100147","journal-title":"J Lipid Res"},{"issue":"6","key":"2892_CR28","doi-asserted-by":"publisher","first-page":"1194","DOI":"10.1016\/j.cell.2013.05.039","volume":"153","author":"C Lopez-Otin","year":"2013","unstructured":"Lopez-Otin C, Blasco MA, Partridge L, Serrano M, Kroemer G (2013) The hallmarks of aging. Cell 153(6):1194\u20131217. https:\/\/doi.org\/10.1016\/j.cell.2013.05.039","journal-title":"Cell"},{"issue":"12","key":"2892_CR29","doi-asserted-by":"publisher","first-page":"550","DOI":"10.1186\/s13059-014-0550-8","volume":"15","author":"MI Love","year":"2014","unstructured":"Love MI, Huber W, Anders S (2014) Moderated estimation of Fold change and dispersion for RNA-seq data with DESeq2. Genome Biol 15(12):550. https:\/\/doi.org\/10.1186\/s13059-014-0550-8","journal-title":"Genome Biol"},{"key":"2892_CR30","doi-asserted-by":"publisher","unstructured":"Martin M (2011) Cutadapt removes adapter sequences from high-throughput sequencing reads. 2011, 17(1), 3%J EMBnet.journal. https:\/\/doi.org\/10.14806\/ej.17.1.200","DOI":"10.14806\/ej.17.1.200"},{"issue":"1","key":"2892_CR31","doi-asserted-by":"publisher","first-page":"7","DOI":"10.1186\/s13024-023-00699-0","volume":"19","author":"A Martirosyan","year":"2024","unstructured":"Martirosyan A, Ansari R, Pestana F, Hebestreit K, Gasparyan H, Aleksanyan R, Holt MG (2024) Unravelling cell type-specific responses to Parkinson\u2019s Disease at single cell resolution. Mol Neurodegener 19(1):7. https:\/\/doi.org\/10.1186\/s13024-023-00699-0","journal-title":"Mol Neurodegener"},{"issue":"6","key":"2892_CR32","doi-asserted-by":"publisher","first-page":"1176","DOI":"10.1016\/j.cmet.2018.05.011","volume":"27","author":"MP Mattson","year":"2018","unstructured":"Mattson MP, Arumugam TV (2018) Hallmarks of Brain Aging: adaptive and pathological modification by Metabolic States. Cell Metab 27(6):1176\u20131199. https:\/\/doi.org\/10.1016\/j.cmet.2018.05.011","journal-title":"Cell Metab"},{"key":"2892_CR33","doi-asserted-by":"publisher","first-page":"148912","DOI":"10.1016\/j.brainres.2024.148912","volume":"1834","author":"L Nicholson","year":"2024","unstructured":"Nicholson L, Piras IS, DeBoth MD, Siniard A, Heras-Garvin A, Stefanova N, Huentelman MJ (2024) Transcriptomic insights into multiple system atrophy from a PLP-alpha-synuclein transgenic mouse model. Brain Res 1834:148912. https:\/\/doi.org\/10.1016\/j.brainres.2024.148912","journal-title":"Brain Res"},{"issue":"7706","key":"2892_CR34","doi-asserted-by":"publisher","first-page":"558","DOI":"10.1038\/s41586-018-0104-4","volume":"557","author":"C Peng","year":"2018","unstructured":"Peng C, Gathagan RJ, Covell DJ, Medellin C, Stieber A, Robinson JL, Lee VM (2018) Cellular milieu imparts distinct pathological alpha-synuclein strains in alpha-synucleinopathies. Nature 557(7706):558\u2013563. https:\/\/doi.org\/10.1038\/s41586-018-0104-4","journal-title":"Nature"},{"issue":"1","key":"2892_CR35","doi-asserted-by":"publisher","first-page":"31","DOI":"10.1093\/hmg\/ddy326","volume":"28","author":"R Pinho","year":"2019","unstructured":"Pinho R, Paiva I, Jercic KG, Fonseca-Ornelas L, Gerhardt E, Fahlbusch C, Outeiro TF (2019) Nuclear localization and phosphorylation modulate pathological effects of alpha-synuclein. Hum Mol Genet 28(1):31\u201350. https:\/\/doi.org\/10.1093\/hmg\/ddy326","journal-title":"Hum Mol Genet"},{"key":"2892_CR37","doi-asserted-by":"publisher","first-page":"263","DOI":"10.3389\/fncel.2019.00263","volume":"13","author":"V Refolo","year":"2019","unstructured":"Refolo V, Stefanova N (2019) Neuroinflammation and glial phenotypic changes in Alpha-Synucleinopathies. Front Cell Neurosci 13:263. https:\/\/doi.org\/10.3389\/fncel.2019.00263","journal-title":"Front Cell Neurosci"},{"issue":"1","key":"2892_CR36","doi-asserted-by":"publisher","first-page":"2","DOI":"10.1186\/s40478-017-0504-y","volume":"6","author":"V Refolo","year":"2018","unstructured":"Refolo V, Bez F, Polissidis A, Kuzdas-Wood D, Sturm E, Kamaratou M, Stefanova N (2018) Progressive striatonigral degeneration in a transgenic mouse model of multiple system atrophy: translational implications for interventional therapies. Acta Neuropathol Commun 6(1):2. https:\/\/doi.org\/10.1186\/s40478-017-0504-y","journal-title":"Acta Neuropathol Commun"},{"issue":"9","key":"2892_CR38","doi-asserted-by":"publisher","first-page":"896","DOI":"10.1038\/nbt.2931","volume":"32","author":"D Risso","year":"2014","unstructured":"Risso D, Ngai J, Speed TP, Dudoit S (2014) Normalization of RNA-seq data using factor analysis of control genes or samples. Nat Biotechnol 32(9):896\u2013902. https:\/\/doi.org\/10.1038\/nbt.2931","journal-title":"Nat Biotechnol"},{"issue":"1","key":"2892_CR39","doi-asserted-by":"publisher","first-page":"38","DOI":"10.1038\/s41531-024-00653-x","volume":"10","author":"I Rosh","year":"2024","unstructured":"Rosh I, Tripathi U, Hussein Y, Rike WA, Djamus J, Shklyar B, Stern S (2024) Synaptic dysfunction and extracellular matrix dysregulation in dopaminergic neurons from sporadic and E326K-GBA1 Parkinson\u2019s disease patients. NPJ Parkinsons Dis 10(1):38. https:\/\/doi.org\/10.1038\/s41531-024-00653-x","journal-title":"NPJ Parkinsons Dis"},{"issue":"3","key":"2892_CR40","doi-asserted-by":"publisher","first-page":"576","DOI":"10.1111\/bpa.12806","volume":"30","author":"EHL Rusholt","year":"2020","unstructured":"Rusholt EHL, Salvesen L, Brudek T, Tesfay B, Pakkenberg B, Olesen MV (2020) Pathological changes in the cerebellum of patients with multiple system atrophy and Parkinson\u2019s disease-a stereological study. Brain Pathol 30(3):576\u2013588. https:\/\/doi.org\/10.1111\/bpa.12806","journal-title":"Brain Pathol"},{"issue":"3","key":"2892_CR41","doi-asserted-by":"publisher","first-page":"e0150705","DOI":"10.1371\/journal.pone.0150705","volume":"11","author":"S Schafferer","year":"2016","unstructured":"Schafferer S, Khurana R, Refolo V, Venezia S, Sturm E, Piatti P, Stefanova N (2016) Changes in the miRNA-mRNA Regulatory Network Precede Motor Symptoms in a mouse model of multiple system atrophy: clinical implications. PLoS ONE 11(3):e0150705. https:\/\/doi.org\/10.1371\/journal.pone.0150705","journal-title":"PLoS ONE"},{"key":"2892_CR42","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-020-2317-6","author":"M Schweighauser","year":"2020","unstructured":"Schweighauser M, Shi Y, Tarutani A, Kametani F, Murzin AG, Ghetti B, Goedert M (2020) Structures of alpha-synuclein filaments from multiple system atrophy. Nature. https:\/\/doi.org\/10.1038\/s41586-020-2317-6","journal-title":"Nature"},{"issue":"7794","key":"2892_CR43","doi-asserted-by":"publisher","first-page":"273","DOI":"10.1038\/s41586-020-1984-7","volume":"578","author":"M Shahnawaz","year":"2020","unstructured":"Shahnawaz M, Mukherjee A, Pritzkow S, Mendez N, Rabadia P, Liu X, Soto C (2020) Discriminating alpha-synuclein strains in Parkinson\u2019s disease and multiple system atrophy. Nature 578(7794):273\u2013277. https:\/\/doi.org\/10.1038\/s41586-020-1984-7","journal-title":"Nature"},{"issue":"2","key":"2892_CR44","doi-asserted-by":"publisher","first-page":"153","DOI":"10.1016\/j.tins.2022.11.007","volume":"46","author":"M Sharma","year":"2023","unstructured":"Sharma M, Burre J (2023) Alpha-synuclein in synaptic function and dysfunction. Trends Neurosci 46(2):153\u2013166. https:\/\/doi.org\/10.1016\/j.tins.2022.11.007","journal-title":"Trends Neurosci"},{"key":"2892_CR45","doi-asserted-by":"publisher","unstructured":"Soles A, Selimovic A, Sbrocco K, Ghannoum F, Hamel K, Moncada EL, Cvetanovic M (2023) Extracellular Matrix Regulation in Physiology and in Brain Disease. Int J Mol Sci 24(8). https:\/\/doi.org\/10.3390\/ijms24087049","DOI":"10.3390\/ijms24087049"},{"issue":"6645","key":"2892_CR46","doi-asserted-by":"publisher","first-page":"839","DOI":"10.1038\/42166","volume":"388","author":"MG Spillantini","year":"1997","unstructured":"Spillantini MG, Schmidt ML, Lee VM, Trojanowski JQ, Jakes R, Goedert M (1997) Alpha-synuclein in Lewy bodies. Nature 388(6645):839\u2013840. https:\/\/doi.org\/10.1038\/42166","journal-title":"Nature"},{"issue":"1","key":"2892_CR47","doi-asserted-by":"publisher","first-page":"117","DOI":"10.1007\/s13311-022-01287-8","volume":"20","author":"N Stefanova","year":"2023","unstructured":"Stefanova N (2023) A mouse model of multiple system atrophy: bench to Bedside. Neurotherapeutics 20(1):117\u2013126. https:\/\/doi.org\/10.1007\/s13311-022-01287-8","journal-title":"Neurotherapeutics"},{"issue":"6","key":"2892_CR52","doi-asserted-by":"publisher","first-page":"334","DOI":"10.1038\/s41583-023-00697-7","volume":"24","author":"N Stefanova","year":"2023","unstructured":"Stefanova N, Wenning GK (2023) Multiple system atrophy: at the crossroads of cellular, molecular and genetic mechanisms. Nat Rev Neurosci 24(6):334\u2013346. https:\/\/doi.org\/10.1038\/s41583-023-00697-7","journal-title":"Nat Rev Neurosci"},{"issue":"3","key":"2892_CR50","doi-asserted-by":"publisher","first-page":"869","DOI":"10.1016\/s0002-9440(10)62307-3","volume":"166","author":"N Stefanova","year":"2005","unstructured":"Stefanova N, Reindl M, Neumann M, Haass C, Poewe W, Kahle PJ, Wenning GK (2005) Oxidative stress in transgenic mice with oligodendroglial alpha-synuclein overexpression replicates the characteristic neuropathology of multiple system atrophy. Am J Pathol 166(3):869\u2013876. https:\/\/doi.org\/10.1016\/s0002-9440(10)62307-3","journal-title":"Am J Pathol"},{"issue":"15","key":"2892_CR51","doi-asserted-by":"publisher","first-page":"2196","DOI":"10.1002\/mds.21671","volume":"22","author":"N Stefanova","year":"2007","unstructured":"Stefanova N, Reindl M, Neumann M, Kahle PJ, Poewe W, Wenning GK (2007) Microglial activation mediates neurodegeneration related to oligodendroglial alpha-synucleinopathy: implications for multiple system atrophy. Mov Disord 22(15):2196\u20132203. https:\/\/doi.org\/10.1002\/mds.21671","journal-title":"Mov Disord"},{"issue":"12","key":"2892_CR48","doi-asserted-by":"publisher","first-page":"1172","DOI":"10.1016\/S1474-4422(09)70288-1","volume":"8","author":"N Stefanova","year":"2009","unstructured":"Stefanova N, Bucke P, Duerr S, Wenning GK (2009) Multiple system atrophy: an update. Lancet Neurol 8(12):1172\u20131178. https:\/\/doi.org\/10.1016\/S1474-4422(09)70288-1","journal-title":"Lancet Neurol"},{"issue":"1","key":"2892_CR49","doi-asserted-by":"publisher","first-page":"51","DOI":"10.1007\/s00401-012-0977-5","volume":"124","author":"N Stefanova","year":"2012","unstructured":"Stefanova N, Kaufmann WA, Humpel C, Poewe W, Wenning GK (2012) Systemic proteasome inhibition triggers neurodegeneration in a transgenic mouse model expressing human alpha-synuclein under oligodendrocyte promoter: implications for multiple system atrophy. Acta Neuropathol 124(1):51\u201365. https:\/\/doi.org\/10.1007\/s00401-012-0977-5","journal-title":"Acta Neuropathol"},{"issue":"2","key":"2892_CR53","doi-asserted-by":"publisher","first-page":"459","DOI":"10.1016\/j.expneurol.2010.05.008","volume":"224","author":"S Stemberger","year":"2010","unstructured":"Stemberger S, Poewe W, Wenning GK, Stefanova N (2010) Targeted overexpression of human alpha-synuclein in oligodendroglia induces lesions linked to MSA-like progressive autonomic failure. Exp Neurol 224(2):459\u2013464. https:\/\/doi.org\/10.1016\/j.expneurol.2010.05.008","journal-title":"Exp Neurol"},{"issue":"11","key":"2892_CR54","doi-asserted-by":"publisher","first-page":"e0294236","DOI":"10.1371\/journal.pone.0294236","volume":"18","author":"D Tang","year":"2023","unstructured":"Tang D, Chen M, Huang X, Zhang G, Zeng L, Zhang G, Wang Y (2023) SRplot: a free online platform for data visualization and graphing. PLoS ONE 18(11):e0294236. https:\/\/doi.org\/10.1371\/journal.pone.0294236","journal-title":"PLoS ONE"},{"issue":"1","key":"2892_CR55","doi-asserted-by":"publisher","first-page":"29","DOI":"10.1186\/s40478-018-0532-2","volume":"6","author":"A Tarutani","year":"2018","unstructured":"Tarutani A, Arai T, Murayama S, Hisanaga SI, Hasegawa M (2018) Potent prion-like behaviors of pathogenic alpha-synuclein and evaluation of inactivation methods. Acta Neuropathol Commun 6(1):29. https:\/\/doi.org\/10.1186\/s40478-018-0532-2","journal-title":"Acta Neuropathol Commun"},{"key":"2892_CR56","doi-asserted-by":"publisher","first-page":"107","DOI":"10.1111\/j.1749-6632.2003.tb07468.x","volume":"991","author":"JQ Trojanowski","year":"2003","unstructured":"Trojanowski JQ, Lee VM (2003) Parkinson\u2019s disease and related alpha-synucleinopathies are brain amyloidoses. Ann N Y Acad Sci 991:107\u2013110. https:\/\/doi.org\/10.1111\/j.1749-6632.2003.tb07468.x","journal-title":"Ann N Y Acad Sci"},{"issue":"3","key":"2892_CR57","doi-asserted-by":"publisher","first-page":"415","DOI":"10.1002\/ana.410440324","volume":"44","author":"PH Tu","year":"1998","unstructured":"Tu PH, Galvin JE, Baba M, Giasson B, Tomita T, Leight S, Lee VM (1998) Glial cytoplasmic inclusions in white matter oligodendrocytes of multiple system atrophy brains contain insoluble alpha-synuclein. Ann Neurol 44(3):415\u2013422. https:\/\/doi.org\/10.1002\/ana.410440324","journal-title":"Ann Neurol"},{"issue":"6","key":"2892_CR58","doi-asserted-by":"publisher","first-page":"977","DOI":"10.1007\/s00401-020-02157-3","volume":"139","author":"A Van der Perren","year":"2020","unstructured":"Van der Perren A, Gelders G, Fenyi A, Bousset L, Brito F, Peelaerts W, Baekelandt V (2020) The structural differences between patient-derived alpha-synuclein strains dictate characteristics of Parkinson\u2019s disease, multiple system atrophy and dementia with Lewy bodies. Acta Neuropathol 139(6):977\u20131000. https:\/\/doi.org\/10.1007\/s00401-020-02157-3","journal-title":"Acta Neuropathol"},{"issue":"3","key":"2892_CR60","doi-asserted-by":"publisher","first-page":"239","DOI":"10.1002\/ana.21465","volume":"64","author":"GK Wenning","year":"2008","unstructured":"Wenning GK, Stefanova N, Jellinger KA, Poewe W, Schlossmacher MG (2008) Multiple system atrophy: a primary oligodendrogliopathy. Ann Neurol 64(3):239\u2013246. https:\/\/doi.org\/10.1002\/ana.21465","journal-title":"Ann Neurol"},{"key":"2892_CR59","doi-asserted-by":"publisher","unstructured":"Wenning GK, Geser F, Krismer F, Seppi K, Duerr S, Boesch S (2013) The natural history of multiple system atrophy: a prospective European cohort study. Lancet Neurol 12(3):264\u2013274. https:\/\/doi.org\/10.1016\/S1474-4422(12)70327-7. European Multiple System Atrophy Study","DOI":"10.1016\/S1474-4422(12)70327-7"},{"issue":"5","key":"2892_CR61","doi-asserted-by":"publisher","first-page":"855","DOI":"10.1007\/s00401-020-02126-w","volume":"139","author":"GP Williams","year":"2020","unstructured":"Williams GP, Marmion DJ, Schonhoff AM, Jurkuvenaite A, Won WJ, Standaert DG, Harms AS (2020) T cell infiltration in both human multiple system atrophy and a novel mouse model of the disease. Acta Neuropathol 139(5):855\u2013874. https:\/\/doi.org\/10.1007\/s00401-020-02126-w","journal-title":"Acta Neuropathol"},{"issue":"3","key":"2892_CR62","doi-asserted-by":"publisher","first-page":"1045","DOI":"10.1074\/jbc.RA118.004471","volume":"294","author":"TR Yamasaki","year":"2019","unstructured":"Yamasaki TR, Holmes BB, Furman JL, Dhavale DD, Su BW, Song ES, Diamond MI (2019) Parkinson\u2019s disease and multiple system atrophy have distinct alpha-synuclein seed characteristics. J Biol Chem 294(3):1045\u20131058. https:\/\/doi.org\/10.1074\/jbc.RA118.004471","journal-title":"J Biol Chem"},{"key":"2892_CR63","doi-asserted-by":"publisher","first-page":"101891","DOI":"10.1016\/j.nicl.2019.101891","volume":"23","author":"H Yang","year":"2019","unstructured":"Yang H, Wang N, Luo X, Lv H, Liu H, Li Y, Fan G (2019) Cerebellar atrophy and its contribution to motor and cognitive performance in multiple system atrophy. Neuroimage Clin 23:101891. https:\/\/doi.org\/10.1016\/j.nicl.2019.101891","journal-title":"Neuroimage Clin"},{"key":"2892_CR64","doi-asserted-by":"publisher","unstructured":"Yang L, Wei M, Xing B, Zhang C (2023) Extracellular matrix and synapse formation. Biosci Rep 43(1). https:\/\/doi.org\/10.1042\/BSR20212411","DOI":"10.1042\/BSR20212411"},{"issue":"1","key":"2892_CR65","doi-asserted-by":"publisher","first-page":"1523","DOI":"10.1038\/s41467-019-09234-6","volume":"10","author":"Y Zhou","year":"2019","unstructured":"Zhou Y, Zhou B, Pache L, Chang M, Khodabakhshi AH, Tanaseichuk O, Chanda SK (2019) Metascape provides a biologist-oriented resource for the analysis of systems-level datasets. Nat Commun 10(1):1523. https:\/\/doi.org\/10.1038\/s41467-019-09234-6","journal-title":"Nat Commun"}],"container-title":["Journal of Neural Transmission"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00702-025-02892-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s00702-025-02892-5","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00702-025-02892-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,27]],"date-time":"2026-05-27T11:51:16Z","timestamp":1779882676000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s00702-025-02892-5"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,2,15]]},"references-count":65,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2026,5]]}},"alternative-id":["2892"],"URL":"https:\/\/doi.org\/10.1007\/s00702-025-02892-5","relation":{},"ISSN":["0300-9564","1435-1463"],"issn-type":[{"value":"0300-9564","type":"print"},{"value":"1435-1463","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,2,15]]},"assertion":[{"value":"26 December 2024","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"3 February 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"15 February 2025","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}}]}}