{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T14:02:19Z","timestamp":1790949739497,"version":"4.1.0"},"reference-count":61,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2025,6,6]],"date-time":"2025-06-06T00:00:00Z","timestamp":1749168000000},"content-version":"vor","delay-in-days":156,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Wellcome Trust Research Training Fellowship","award":["203646\/Z\/16\/Z"],"award-info":[{"award-number":["203646\/Z\/16\/Z"]}]},{"DOI":"10.13039\/501100000272","name":"National Institute for Health and Care Research","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000272","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100007155","name":"Medical Research Council","doi-asserted-by":"publisher","award":["MR\/J012831\/1"],"award-info":[{"award-number":["MR\/J012831\/1"]}],"id":[{"id":"10.13039\/501100007155","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,4,30]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Point mutations in the SNCA gene, which encodes \u03b1-synuclein (\u03b1Syn), are a known cause of familial Parkinson\u2019s disease. The glycine-51-aspartic acid (G51D) mutation causes early-onset neurodegeneration with complex, wide-spread \u03b1Syn pathology. We used CRISPR\/Cas9 gene editing to introduce the G51D point mutation into the endogenous rat Snca gene. Our goal was to investigate whether the G51D \u03b1Syn mutation gives rise to synucleinopathy and neurodegenerative phenotypes in rats. Co-localisation immunostaining studies with synaptic proteins revealed that \u03b1SynG51D protein fails to efficiently localise to synapses. Furthermore, biochemical isolation of synaptosomes from rat cortex demonstrated a significant depletion of \u03b1Syn in SncaG51D\/+ and SncaG51D\/G51D rats. Unbiased proteomic investigation of the cortex identified significant synaptic dysregulation in SncaG51D\/G51D animals. Finally, we compared the propensity for synucleinopathy of Snca+\/+ and SncaG51D\/G51D rats by stereotaxically delivering \u03b1Syn pre-formed fibrils (PFFs) into the pre-frontal cortex. At an early time-point, 6 weeks post-injection, we observed discrete Lewy pathology-like structures positive for phosphoserine-129-\u03b1Syn (pS129-\u03b1Syn) only in SncaG51D\/G51D brains. At 26 weeks post-injection of PFFs, SncaG51D\/G51D brains exhibited intense, discrete pS129-\u03b1Syn-positive structures, while Snca+\/+ brains exhibited diffuse pS129-\u03b1Syn immunostaining. In summary, G51D mutagenesis of the endogenous Snca rat gene caused reduced synaptic localisation of \u03b1Syn, proteomic evidence of early synaptic dysfunction, and enhanced propensity for \u03b1Syn pathology.<\/jats:p>","DOI":"10.1093\/braincomms\/fcaf224","type":"journal-article","created":{"date-parts":[[2025,6,6]],"date-time":"2025-06-06T17:30:06Z","timestamp":1749231006000},"source":"Crossref","is-referenced-by-count":1,"title":["Glycine-to-aspartic acid mutation at codon 51 in <i>Snca<\/i> disrupts the synaptic localisation of \u03b1-synuclein and enhances its propensity for synucleinopathy"],"prefix":"10.1093","volume":"7","author":[{"given":"Stephen","family":"West","sequence":"first","affiliation":[{"name":"Centre for Regenerative Medicine, Institute for Regeneration and Repair, The University of Edinburgh , Edinburgh EH16 4UU ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ammar","family":"Natalwala","sequence":"additional","affiliation":[{"name":"Centre for Regenerative Medicine, Institute for Regeneration and Repair, The University of Edinburgh , Edinburgh EH16 4UU ,","place":["UK"]},{"name":"Department of Neuromuscular Diseases, UCL Queen Square Institute of Neurology, Queen Square House , London WC1N 3BG ,","place":["UK"]},{"name":"Victor Horsley Department of Neurosurgery, National Hospital for Neurology and Neurosurgery, Queen Square , London WC1N 3BG ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0584-7505","authenticated-orcid":false,"given":"Karamjit","family":"Singh Dolt","sequence":"additional","affiliation":[{"name":"Centre for Regenerative Medicine, Institute for Regeneration and Repair, The University of Edinburgh , Edinburgh EH16 4UU ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Douglas J","family":"Lamont","sequence":"additional","affiliation":[{"name":"FingerPrints Proteomics Facility, School of Life Sciences, University of Dundee , Dundee DD1 5EH ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melanie","family":"McMillan","sequence":"additional","affiliation":[{"name":"Centre for Reproductive Health, Institute for Regeneration and Repair, The University of Edinburgh , Edinburgh EH16 4UU ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6591-6269","authenticated-orcid":false,"given":"Kelvin","family":"Luk","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, Center for Neurodegenerative Disease Research, Alzheimer's Disease Core Center, Institute on Aging, University of Pennsylvania Perelman School of Medicine , Philadelphia, PA 19104-2676 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomoji","family":"Mashimo","sequence":"additional","affiliation":[{"name":"Division of Animal Genetics, Laboratory Animal Research Center, Institute of Medical Science, The University of Tokyo , Minato-ku, Tokyo 108-8639 ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8805-7356","authenticated-orcid":false,"given":"Tilo","family":"Kunath","sequence":"additional","affiliation":[{"name":"Centre for Regenerative Medicine, Institute for Regeneration and Repair, The University of Edinburgh , Edinburgh EH16 4UU ,","place":["UK"]},{"name":"School of Biological Sciences, Institute for Stem Cell Research, The University of Edinburgh , Edinburgh EH16 4UU ,","place":["UK"]},{"name":"Centre for Engineering Biology, The University of Edinburgh , Edinburgh EH9 3BF ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2025,6,6]]},"reference":[{"issue":"5646","key":"2025062605151195300_fcaf224-B1","doi-asserted-by":"crossref","first-page":"841","DOI":"10.1126\/science.1090278","article-title":"alpha-synuclein locus triplication causes Parkinson\u2019s disease","volume":"302","author":"Singleton","year":"2003","journal-title":"Science"},{"issue":"9440","key":"2025062605151195300_fcaf224-B2","doi-asserted-by":"crossref","first-page":"1167","DOI":"10.1016\/S0140-6736(04)17103-1","article-title":"Alpha-synuclein locus duplication as a cause of familial Parkinson\u2019s disease","volume":"364","author":"Chartier-Harlin","year":"2004","journal-title":"Lancet"},{"issue":"5290","key":"2025062605151195300_fcaf224-B3","doi-asserted-by":"crossref","first-page":"1197","DOI":"10.1126\/science.274.5290.1197","article-title":"Mapping of a gene for Parkinson\u2019s disease to chromosome 4q21-q23","volume":"274","author":"Polymeropoulos","year":"1996","journal-title":"Science"},{"issue":"2","key":"2025062605151195300_fcaf224-B4","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1038\/ng0298-106","article-title":"Ala30Pro mutation in the gene encoding alpha-synuclein in Parkinson\u2019s disease","volume":"18","author":"Kr\u00fcger","year":"1998","journal-title":"Nat Genet"},{"issue":"2","key":"2025062605151195300_fcaf224-B5","doi-asserted-by":"crossref","first-page":"164","DOI":"10.1002\/ana.10795","article-title":"The new mutation, E46K, of alpha-synuclein causes Parkinson and Lewy body dementia","volume":"55","author":"Zarranz","year":"2004","journal-title":"Ann Neurol"},{"issue":"9","key":"2025062605151195300_fcaf224-B6","doi-asserted-by":"crossref","first-page":"2180.e1","DOI":"10.1016\/j.neurobiolaging.2014.03.024","article-title":"Novel \u03b1-synuclein mutation A53E associated with atypical multiple system atrophy and Parkinson\u2019s disease-type pathology","volume":"35","author":"Pasanen","year":"2014","journal-title":"Neurobiol Aging"},{"key":"2025062605151195300_fcaf224-B7","doi-asserted-by":"crossref","first-page":"248.e7","DOI":"10.1016\/j.neurobiolaging.2017.05.022","article-title":"Homozygous alpha-synuclein p.A53V in familial Parkinson\u2019s disease","volume":"57","author":"Yoshino","year":"2017","journal-title":"Neurobiol Aging"},{"issue":"6","key":"2025062605151195300_fcaf224-B8","doi-asserted-by":"crossref","first-page":"620","DOI":"10.1111\/neup.12687","article-title":"A novel SNCA E83Q mutation in a case of dementia with Lewy bodies and atypical frontotemporal lobar degeneration","volume":"40","author":"Kapasi","year":"2020","journal-title":"Neuropathology"},{"issue":"7","key":"2025062605151195300_fcaf224-B9","doi-asserted-by":"crossref","first-page":"1624","DOI":"10.1002\/mds.28534","article-title":"A novel SNCA A30G mutation causes familial Parkinson\u2019s disease","volume":"36","author":"Liu","year":"2021","journal-title":"Mov Disord"},{"issue":"5","key":"2025062605151195300_fcaf224-B10","doi-asserted-by":"crossref","first-page":"753","DOI":"10.1007\/s00401-013-1096-7","article-title":"\u03b1-Synucleinopathy associated with G51D SNCA mutation: A link between Parkinson\u2019s disease and multiple system atrophy?","volume":"125","author":"Kiely","year":"2013","journal-title":"Acta Neuropathol"},{"issue":"4","key":"2025062605151195300_fcaf224-B11","doi-asserted-by":"crossref","first-page":"459","DOI":"10.1002\/ana.23894","article-title":"G51d \u03b1-synuclein mutation causes a novel parkinsonian-pyramidal syndrome","volume":"73","author":"Lesage","year":"2013","journal-title":"Ann Neurol"},{"issue":"2","key":"2025062605151195300_fcaf224-B12","doi-asserted-by":"crossref","first-page":"262","DOI":"10.1016\/j.parkreldis.2013.11.008","article-title":"Clinical and neuroimaging features of patient with early-onset Parkinson\u2019s disease with dementia carrying SNCA p.G51D mutation","volume":"20","author":"Tokutake","year":"2014","journal-title":"Parkinsonism Relat Disord"},{"key":"2025062605151195300_fcaf224-B13","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1186\/s13024-015-0038-3","article-title":"Distinct clinical and neuropathological features of G51D SNCA mutation cases compared with SNCA duplication and H50Q mutation","volume":"10","author":"Kiely","year":"2015","journal-title":"Mol Neurodegener"},{"issue":"11","key":"2025062605151195300_fcaf224-B14","doi-asserted-by":"crossref","first-page":"2628","DOI":"10.1021\/acschemneuro.8b00107","article-title":"Parkinson\u2019s disease associated \u03b1-synuclein familial mutants promote dopaminergic neuronal death in Drosophila melanogaster","volume":"9","author":"Mohite","year":"2018","journal-title":"ACS Chem Neurosci"},{"issue":"1","key":"2025062605151195300_fcaf224-B15","doi-asserted-by":"crossref","first-page":"12420","DOI":"10.1038\/s41598-018-30436-3","article-title":"CRISPR\/Cas9-mediated generation of guangxi bama minipigs harboring three mutations in \u03b1-synuclein causing Parkinson\u2019s disease","volume":"8","author":"Zhu","year":"2018","journal-title":"Sci Rep"},{"key":"2025062605151195300_fcaf224-B16","doi-asserted-by":"crossref","first-page":"1095761","DOI":"10.3389\/fnins.2023.1095761","article-title":"In vivo18F-DOPA PET imaging identifies a dopaminergic deficit in a rat model with a G51D \u03b1-synuclein mutation","volume":"17","author":"Morley","year":"2023","journal-title":"Front Neurosci"},{"issue":"Pt 2","key":"2025062605151195300_fcaf224-B17","doi-asserted-by":"crossref","first-page":"412","DOI":"10.1093\/brain\/aws358","article-title":"A progressive dopaminergic phenotype associated with neurotoxic conversion of \u03b1-synuclein in BAC-transgenic rats","volume":"136","author":"Nuber","year":"2013","journal-title":"Brain"},{"issue":"2","key":"2025062605151195300_fcaf224-B18","doi-asserted-by":"crossref","first-page":"232","DOI":"10.1097\/00004647-200202000-00011","article-title":"Increase in dopamine turnover occurs early in Parkinson\u2019s disease: Evidence from a new modeling approach to PET 18 F-fluorodopa data","volume":"22","author":"Sossi","year":"2002","journal-title":"J Cereb Blood Flow Metab"},{"issue":"16","key":"2025062605151195300_fcaf224-B19","doi-asserted-by":"crossref","first-page":"2717","DOI":"10.1002\/mds.23356","article-title":"Dopamine turnover increases in asymptomatic LRRK2 mutations carriers","volume":"25","author":"Sossi","year":"2010","journal-title":"Mov Disord"},{"issue":"4","key":"2025062605151195300_fcaf224-B20","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1002\/1531-8249(200004)47:4<493::AID-ANA13>3.0.CO;2-4","article-title":"In vivo positron emission tomographic evidence for compensatory changes in presynaptic dopaminergic nerve terminals in Parkinson\u2019s disease","volume":"47","author":"Lee","year":"2000","journal-title":"Ann Neurol"},{"issue":"8","key":"2025062605151195300_fcaf224-B21","doi-asserted-by":"crossref","first-page":"869","DOI":"10.1097\/01.WCB.0000126563.85360.75","article-title":"Changes of dopamine turnover in the progression of Parkinson\u2019s disease as measured by positron emission tomography: Their relation to disease-compensatory mechanisms","volume":"24","author":"Sossi","year":"2004","journal-title":"J Cereb Blood Flow Metab"},{"issue":"Pt 8","key":"2025062605151195300_fcaf224-B22","doi-asserted-by":"crossref","first-page":"2419","DOI":"10.1093\/brain\/awt192","article-title":"Disease duration and the integrity of the nigrostriatal system in Parkinson\u2019s disease","volume":"136","author":"Kordower","year":"2013","journal-title":"Brain"},{"issue":"6","key":"2025062605151195300_fcaf224-B23","doi-asserted-by":"crossref","first-page":"873","DOI":"10.1002\/ana.25103","article-title":"Striatal dopamine in Parkinson disease: A meta-analysis of imaging studies","volume":"82","author":"Kaasinen","year":"2017","journal-title":"Ann Neurol"},{"issue":"17","key":"2025062605151195300_fcaf224-B24","doi-asserted-by":"crossref","first-page":"4491","DOI":"10.1093\/hmg\/ddu165","article-title":"The novel Parkinson\u2019s disease linked mutation G51D attenuates in vitro aggregation and membrane binding of \u03b1-synuclein, and enhances its secretion and nuclear localization in cells","volume":"23","author":"Fares","year":"2014","journal-title":"Hum Mol Genet"},{"issue":"19","key":"2025062605151195300_fcaf224-B25","doi-asserted-by":"crossref","first-page":"16873","DOI":"10.1074\/jbc.M210136200","article-title":"Lipid binding inhibits alpha-synuclein fibril formation","volume":"278","author":"Zhu","year":"2003","journal-title":"J Biol Chem"},{"key":"2025062605151195300_fcaf224-B26","first-page":"480","volume-title":"The rat brain in stereotaxic coordinates","author":"Paxinos","year":"2013","edition":"7th ed"},{"issue":"1","key":"2025062605151195300_fcaf224-B27","doi-asserted-by":"crossref","first-page":"16878","DOI":"10.1038\/s41598-017-17204-5","article-title":"Qupath: Open source software for digital pathology image analysis","volume":"7","author":"Bankhead","year":"2017","journal-title":"Sci Rep"},{"issue":"1","key":"2025062605151195300_fcaf224-B28","doi-asserted-by":"crossref","first-page":"12412","DOI":"10.1038\/s41598-017-12603-0","article-title":"Proteomic mapping of differentially vulnerable pre-synaptic populations identifies regulators of neuronal stability in vivo","volume":"7","author":"Llavero Hurtado","year":"2017","journal-title":"Sci Rep"},{"issue":"D1","key":"2025062605151195300_fcaf224-B29","doi-asserted-by":"crossref","first-page":"D543","DOI":"10.1093\/nar\/gkab1038","article-title":"The PRIDE database resources in 2022: A hub for mass spectrometry-based proteomics evidences","volume":"50","author":"Perez-Riverol","year":"2022","journal-title":"Nucleic Acids Res"},{"issue":"W1","key":"2025062605151195300_fcaf224-B30","doi-asserted-by":"crossref","first-page":"W191","DOI":"10.1093\/nar\/gkz369","article-title":"G:Profiler: A web server for functional enrichment analysis and conversions of gene lists (2019 update)","volume":"47","author":"Raudvere","year":"2019","journal-title":"Nucleic Acids Res"},{"issue":"D1","key":"2025062605151195300_fcaf224-B31","doi-asserted-by":"crossref","first-page":"D590","DOI":"10.1093\/nar\/gky962","article-title":"New approach for understanding genome variations in KEGG","volume":"47","author":"Kanehisa","year":"2019","journal-title":"Nucleic Acids Res"},{"issue":"12","key":"2025062605151195300_fcaf224-B32","doi-asserted-by":"crossref","first-page":"7619","DOI":"10.1074\/jbc.274.12.7619","article-title":"Mutant and wild type human alpha-synucleins assemble into elongated filaments with distinct morphologies in vitro","volume":"274","author":"Giasson","year":"1999","journal-title":"J Biol Chem"},{"issue":"47","key":"2025062605151195300_fcaf224-B33","doi-asserted-by":"crossref","first-page":"20051","DOI":"10.1073\/pnas.0908005106","article-title":"Exogenous alpha-synuclein fibrils seed the formation of Lewy body-like intracellular inclusions in cultured cells","volume":"106","author":"Luk","year":"2009","journal-title":"Proc Natl Acad Sci U S A."},{"issue":"5","key":"2025062605151195300_fcaf224-B34","doi-asserted-by":"crossref","first-page":"975","DOI":"10.1084\/jem.20112457","article-title":"Intracerebral inoculation of pathological \u03b1-synuclein initiates a rapidly progressive neurodegenerative \u03b1-synucleinopathy in mice","volume":"209","author":"Luk","year":"2012","journal-title":"J Exp Med"},{"issue":"8","key":"2025062605151195300_fcaf224-B35","doi-asserted-by":"crossref","first-page":"2111","DOI":"10.1016\/j.celrep.2019.07.060","article-title":"Complement C3 is activated in human AD brain and is required for neurodegeneration in mouse models of amyloidosis and tauopathy","volume":"28","author":"Wu","year":"2019","journal-title":"Cell Rep"},{"key":"2025062605151195300_fcaf224-B36","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1186\/1742-2094-3-29","article-title":"Complement activation in the Parkinson\u2019s disease substantia nigra: An immunocytochemical study","volume":"3","author":"Loeffler","year":"2006","journal-title":"J Neuroinflammation"},{"issue":"1","key":"2025062605151195300_fcaf224-B37","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1186\/s12974-021-02225-9","article-title":"Alpha-synuclein activates the classical complement pathway and mediates complement-dependent cell toxicity","volume":"18","author":"Gregersen","year":"2021","journal-title":"J Neuroinflammation"},{"issue":"7","key":"2025062605151195300_fcaf224-B38","doi-asserted-by":"crossref","first-page":"3428","DOI":"10.1021\/acs.jproteome.0c01002","article-title":"Complement and coagulation cascades are potentially involved in dopaminergic neurodegeneration in \u03b1-synuclein-based mouse models of Parkinson\u2019s disease","volume":"20","author":"Ma","year":"2021","journal-title":"J Proteome Res"},{"issue":"9","key":"2025062605151195300_fcaf224-B39","doi-asserted-by":"crossref","first-page":"1223","DOI":"10.1001\/archneur.60.9.1223","article-title":"Positron emission tomography of striatal serotonin transporters in Parkinson disease","volume":"60","author":"Kerenyi","year":"2003","journal-title":"Arch Neurol"},{"issue":"2","key":"2025062605151195300_fcaf224-B40","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1002\/ana.24859","article-title":"Serotonin transporter in Parkinson\u2019s disease: A meta-analysis of positron emission tomography studies","volume":"81","author":"Pagano","year":"2017","journal-title":"Ann Neurol"},{"issue":"52","key":"2025062605151195300_fcaf224-B41","doi-asserted-by":"crossref","first-page":"22474","DOI":"10.1073\/pnas.0912193106","article-title":"Functional enhancement and protection of dopaminergic terminals by RAB3B overexpression","volume":"106","author":"Chung","year":"2009","journal-title":"Proc Natl Acad Sci U S A."},{"issue":"Suppl 1","key":"2025062605151195300_fcaf224-B42","doi-asserted-by":"crossref","first-page":"S16","DOI":"10.1016\/j.parkreldis.2015.08.015","article-title":"Phenotypic spectrum of alpha-synuclein mutations: New insights from patients and cellular models","volume":"22","author":"Petrucci","year":"2016","journal-title":"Parkinsonism Relat Disord"},{"key":"2025062605151195300_fcaf224-B43","doi-asserted-by":"crossref","first-page":"440","DOI":"10.1038\/ncomms1453","article-title":"Parkinson\u2019s disease induced pluripotent stem cells with triplication of the \u03b1-synuclein locus","volume":"2","author":"Devine","year":"2011","journal-title":"Nat Commun"},{"issue":"1","key":"2025062605151195300_fcaf224-B44","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1038\/s41531-024-00662-w","article-title":"Generation of G51D and 3D mice reveals decreased \u03b1-synuclein tetramer-monomer ratios promote Parkinson\u2019s disease phenotypes","volume":"10","author":"Nuber","year":"2024","journal-title":"npj Parkinsons Dis"},{"issue":"39","key":"2025062605151195300_fcaf224-B45","doi-asserted-by":"crossref","first-page":"e2406479121","DOI":"10.1073\/pnas.2406479121","article-title":"Olfactory deficit and gastrointestinal dysfunction precede motor abnormalities in alpha-synuclein G51D knock-in mice","volume":"121","author":"Kim","year":"2024","journal-title":"Proc Natl Acad Sci U S A."},{"key":"2025062605151195300_fcaf224-B46","doi-asserted-by":"crossref","first-page":"150","DOI":"10.1016\/j.nbd.2015.04.007","article-title":"Effects of impaired membrane interactions on \u03b1-synuclein aggregation and neurotoxicity","volume":"79","author":"Ysselstein","year":"2015","journal-title":"Neurobiol Dis"},{"issue":"6","key":"2025062605151195300_fcaf224-B47","doi-asserted-by":"crossref","first-page":"909","DOI":"10.1021\/acschemneuro.9b00594","article-title":"The properties of \u03b1-synuclein secondary nuclei are dominated by the solution conditions rather than the seed fibril strain","volume":"11","author":"Peduzzo","year":"2020","journal-title":"ACS Chem Neurosci"},{"issue":"1","key":"2025062605151195300_fcaf224-B48","doi-asserted-by":"crossref","first-page":"6252","DOI":"10.1038\/s41467-021-26433-2","article-title":"The hereditary mutation G51D unlocks a distinct fibril strain transmissible to wild-type \u03b1-synuclein","volume":"12","author":"Sun","year":"2021","journal-title":"Nat Commun"},{"issue":"6","key":"2025062605151195300_fcaf224-B49","doi-asserted-by":"crossref","first-page":"977","DOI":"10.1007\/s00401-020-02157-3","article-title":"The structural differences between patient-derived \u03b1-synuclein strains dictate characteristics of Parkinson\u2019s disease, multiple system atrophy and dementia with Lewy bodies","volume":"139","author":"Van der Perren","year":"2020","journal-title":"Acta Neuropathol"},{"issue":"Pt 3","key":"2025062605151195300_fcaf224-B50","doi-asserted-by":"crossref","first-page":"871","DOI":"10.1093\/brain\/awv403","article-title":"GABA transmission via ATP-dependent K+ channels regulates \u03b1-synuclein secretion in mouse striatum","volume":"139","author":"Emmanouilidou","year":"2016","journal-title":"Brain"},{"issue":"46","key":"2025062605151195300_fcaf224-B51","doi-asserted-by":"crossref","first-page":"16859","DOI":"10.1073\/pnas.0503783102","article-title":"RNA splicing capability of live neuronal dendrites","volume":"102","author":"Glanzer","year":"2005","journal-title":"Proc Natl Acad Sci U S A."},{"issue":"3","key":"2025062605151195300_fcaf224-B52","doi-asserted-by":"crossref","first-page":"387","DOI":"10.1002\/glia.22611","article-title":"Alpha-synuclein transfers from neurons to oligodendrocytes","volume":"62","author":"Reyes","year":"2014","journal-title":"Glia"},{"issue":"8","key":"2025062605151195300_fcaf224-B53","doi-asserted-by":"crossref","first-page":"1252","DOI":"10.1016\/j.celrep.2015.01.060","article-title":"Progressive aggregation of alpha-synuclein and selective degeneration of Lewy inclusion-bearing neurons in a mouse model of parkinsonism","volume":"10","author":"Osterberg","year":"2015","journal-title":"Cell Rep"},{"key":"2025062605151195300_fcaf224-B54","doi-asserted-by":"crossref","first-page":"116","DOI":"10.1016\/j.brainresbull.2018.10.003","article-title":"Cerebral inoculation of human A53T \u03b1-synuclein reduces spatial memory decline and amyloid-\u03b2 aggregation in APP\/PS1 transgenic mice of Alzheimer\u2019s disease","volume":"143","author":"Hao","year":"2018","journal-title":"Brain Res Bull"},{"issue":"1","key":"2025062605151195300_fcaf224-B55","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1186\/s40478-019-0733-3","article-title":"Comparative analyses of the in vivo induction and transmission of \u03b1-synuclein pathology in transgenic mice by MSA brain lysate and recombinant \u03b1-synuclein fibrils","volume":"7","author":"Dhillon","year":"2019","journal-title":"Acta Neuropathol Commun"},{"issue":"2","key":"2025062605151195300_fcaf224-B56","doi-asserted-by":"crossref","first-page":"260","DOI":"10.1016\/j.neuron.2019.10.010","article-title":"Amyloid-Beta (A\u03b2) plaques promote seeding and spreading of alpha-synuclein and tau in a mouse model of Lewy body disorders with a\u03b2 pathology","volume":"105","author":"Bassil","year":"2020","journal-title":"Neuron"},{"issue":"28","key":"2025062605151195300_fcaf224-B57","doi-asserted-by":"crossref","first-page":"9364","DOI":"10.1523\/JNEUROSCI.4787-13.2014","article-title":"Synucleins regulate the kinetics of synaptic vesicle endocytosis","volume":"34","author":"Vargas","year":"2014","journal-title":"J Neurosci"},{"key":"2025062605151195300_fcaf224-B58","doi-asserted-by":"crossref","first-page":"898560","DOI":"10.3389\/fcell.2022.898560","article-title":"An isogenic collection of pluripotent stem cell lines with elevated \u03b1-synuclein expression validated for neural induction and cortical neuron differentiation","volume":"10","author":"Natalwala","year":"2022","journal-title":"Front Cell Dev Biol"},{"key":"2025062605151195300_fcaf224-B59","doi-asserted-by":"crossref","first-page":"136077","DOI":"10.1016\/j.neulet.2021.136077","article-title":"Physicochemical characterization of the G51D mutation of \u03b1-synuclein that is responsible for its severe cytotoxicity","volume":"760","author":"Murata","year":"2021","journal-title":"Neurosci Lett"},{"issue":"4","key":"2025062605151195300_fcaf224-B60","doi-asserted-by":"crossref","first-page":"1293","DOI":"10.3390\/molecules27041293","article-title":"The pathological G51D mutation in alpha-synuclein oligomers confers distinct structural attributes and cellular toxicity","volume":"27","author":"Xu","year":"2022","journal-title":"Molecules"},{"issue":"2","key":"2025062605151195300_fcaf224-B61","doi-asserted-by":"crossref","first-page":"256","DOI":"10.1002\/mds.27887","article-title":"Structurally distinct \u03b1-synuclein fibrils induce robust parkinsonian pathology","volume":"35","author":"Hayakawa","year":"2020","journal-title":"Mov Disord"}],"container-title":["Brain Communications"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/braincomms\/advance-article-pdf\/doi\/10.1093\/braincomms\/fcaf224\/63447021\/fcaf224.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/braincomms\/article-pdf\/7\/3\/fcaf224\/63447021\/fcaf224.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/braincomms\/article-pdf\/7\/3\/fcaf224\/63447021\/fcaf224.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,6,26]],"date-time":"2025-06-26T09:15:24Z","timestamp":1750929324000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/braincomms\/article\/doi\/10.1093\/braincomms\/fcaf224\/8157954"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025]]},"references-count":61,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2025,4,30]]}},"URL":"https:\/\/doi.org\/10.1093\/braincomms\/fcaf224","relation":{},"ISSN":["2632-1297"],"issn-type":[{"value":"2632-1297","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2025]]},"published":{"date-parts":[[2025]]},"article-number":"fcaf224"}}