{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T13:16:23Z","timestamp":1791983783481,"version":"4.4.0"},"reference-count":78,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2019,12,9]],"date-time":"2019-12-09T00:00:00Z","timestamp":1575849600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"DOI":"10.13039\/501100001700","name":"Ministry of Education, Culture, Sports, Science, and Technology","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100001700","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Scientific Research","award":["JP18H04041"],"award-info":[{"award-number":["JP18H04041"]}]},{"name":"Scientific Research on Innovative Areas","award":["JP17H05698"],"award-info":[{"award-number":["JP17H05698"]}]},{"name":"Integrated Neurotechnologies for Disease Studies (Brain\/MINDS) from Japan Agency for Medical Research and Development","award":["JP18dm0207020"],"award-info":[{"award-number":["JP18dm0207020"]}]},{"name":"Integrated Neurotechnologies for Disease Studies (Brain\/MINDS) from Japan Agency for Medical Research and Development","award":["JP18dm0207024"],"award-info":[{"award-number":["JP18dm0207024"]}]},{"DOI":"10.13039\/501100002241","name":"Japan Science and Technology Agency","doi-asserted-by":"publisher","award":["JP17gm0710011"],"award-info":[{"award-number":["JP17gm0710011"]}],"id":[{"id":"10.13039\/501100002241","id-type":"DOI","asserted-by":"publisher"}]},{"name":"JSPS KAKENHI","award":["JP14616060"],"award-info":[{"award-number":["JP14616060"]}]},{"DOI":"10.13039\/501100004398","name":"Mitsubishi foundation","doi-asserted-by":"publisher","award":["29125"],"award-info":[{"award-number":["29125"]}],"id":[{"id":"10.13039\/501100004398","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2020,1,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Parkinson\u2019s disease is one of the most common movement disorders and is characterized by dopaminergic cell loss and the accumulation of pathological \u03b1-synuclein, but its precise pathogenetic mechanisms remain elusive. To develop disease-modifying therapies for Parkinson\u2019s disease, an animal model that recapitulates the pathology and symptoms of the disease, especially in the prodromal stage, is indispensable. As subjects with \u03b1-synuclein gene (SNCA) multiplication as well as point mutations develop familial Parkinson\u2019s disease and a genome-wide association study in Parkinson\u2019s disease has identified SNCA as a risk gene for Parkinson\u2019s disease, the increased expression of \u03b1-synuclein is closely associated with the aetiology of Parkinson\u2019s disease. In this study we generated bacterial artificial chromosome transgenic mice harbouring SNCA and its gene expression regulatory regions in order to maintain the native expression pattern of \u03b1-synuclein. Furthermore, to enhance the pathological properties of \u03b1-synuclein, we inserted into SNCA an A53T mutation, two single-nucleotide polymorphisms identified in a genome-wide association study in Parkinson\u2019s disease and a Rep1 polymorphism, all of which are causal of familial Parkinson\u2019s disease or increase the risk of sporadic Parkinson\u2019s disease. These A53T SNCA bacterial artificial chromosome transgenic mice showed an expression pattern of human \u03b1-synuclein very similar to that of endogenous mouse \u03b1-synuclein. They expressed truncated, oligomeric and proteinase K-resistant phosphorylated forms of \u03b1-synuclein in the regions that are specifically affected in Parkinson\u2019s disease and\/or dementia with Lewy bodies, including the olfactory bulb, cerebral cortex, striatum and substantia nigra. Surprisingly, these mice exhibited rapid eye movement (REM) sleep without atonia, which is a key feature of REM sleep behaviour disorder, at as early as 5 months of age. Consistent with this observation, the REM sleep-regulating neuronal populations in the lower brainstem, including the sublaterodorsal tegmental nucleus, nuclei in the ventromedial medullary reticular formation and the pedunculopontine nuclei, expressed phosphorylated \u03b1-synuclein. In addition, they also showed hyposmia at 9 months of age, which is consistent with the significant accumulation of phosphorylated \u03b1-synuclein in the olfactory bulb. The dopaminergic neurons in the substantia nigra pars compacta degenerated, and their number was decreased in an age-dependent manner by up to 17.1% at 18 months of age compared to wild-type, although the mice did not show any related locomotor dysfunction. In conclusion, we created a novel mouse model of prodromal Parkinson\u2019s disease that showed RBD-like behaviour and hyposmia without motor symptoms.<\/jats:p>","DOI":"10.1093\/brain\/awz380","type":"journal-article","created":{"date-parts":[[2019,11,18]],"date-time":"2019-11-18T09:07:58Z","timestamp":1574068078000},"page":"249-265","source":"Crossref","is-referenced-by-count":118,"title":["\u03b1-Synuclein BAC transgenic mice exhibit RBD-like behaviour and hyposmia: a prodromal Parkinson\u2019s disease model"],"prefix":"10.1093","volume":"143","author":[{"given":"Tomoyuki","family":"Taguchi","sequence":"first","affiliation":[{"name":"Department of Neurology Kyoto University Graduate School of Medicine, Kyoto, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masashi","family":"Ikuno","sequence":"additional","affiliation":[{"name":"Department of Neurology Kyoto University Graduate School of Medicine, Kyoto, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mari","family":"Hondo","sequence":"additional","affiliation":[{"name":"International Institute for Integrative Sleep Medicine (WPI-IIIS), The University of Tsukuba, Ibaraki, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laxmi Kumar","family":"Parajuli","sequence":"additional","affiliation":[{"name":"Department of Cell Biology and Neuroscience, Juntendo University Graduate School of Medicine, Tokyo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katsutoshi","family":"Taguchi","sequence":"additional","affiliation":[{"name":"Department of Anatomy and Neurobiology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Ueda","sequence":"additional","affiliation":[{"name":"Department of Neurology Kyoto University Graduate School of Medicine, Kyoto, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masanori","family":"Sawamura","sequence":"additional","affiliation":[{"name":"Department of Neurology Kyoto University Graduate School of Medicine, Kyoto, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1444-9381","authenticated-orcid":false,"given":"Shinya","family":"Okuda","sequence":"additional","affiliation":[{"name":"Department of Neurology Kyoto University Graduate School of Medicine, Kyoto, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Etsuro","family":"Nakanishi","sequence":"additional","affiliation":[{"name":"Department of Neurology Kyoto University Graduate School of Medicine, Kyoto, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junko","family":"Hara","sequence":"additional","affiliation":[{"name":"Department of Neurology Kyoto University Graduate School of Medicine, Kyoto, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Norihito","family":"Uemura","sequence":"additional","affiliation":[{"name":"Department of Neurology Kyoto University Graduate School of Medicine, Kyoto, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yusuke","family":"Hatanaka","sequence":"additional","affiliation":[{"name":"Department of Neurology Kyoto University Graduate School of Medicine, Kyoto, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takashi","family":"Ayaki","sequence":"additional","affiliation":[{"name":"Department of Neurology Kyoto University Graduate School of Medicine, Kyoto, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7792-1487","authenticated-orcid":false,"given":"Shuichi","family":"Matsuzawa","sequence":"additional","affiliation":[{"name":"Department of Neurology Kyoto University Graduate School of Medicine, Kyoto, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masaki","family":"Tanaka","sequence":"additional","affiliation":[{"name":"Department of Anatomy and Neurobiology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Omar M A","family":"El-Agnaf","sequence":"additional","affiliation":[{"name":"Neurological Disorders Research Center, Qatar Biomedical Research Institute (QBRI), Hamad Bin Khalifa University (HBKU), Qatar Foundation, Doha, Qatar"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masato","family":"Koike","sequence":"additional","affiliation":[{"name":"Department of Cell Biology and Neuroscience, Juntendo University Graduate School of Medicine, Tokyo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masashi","family":"Yanagisawa","sequence":"additional","affiliation":[{"name":"International Institute for Integrative Sleep Medicine (WPI-IIIS), The University of Tsukuba, Ibaraki, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8356-1409","authenticated-orcid":false,"given":"Maiko T","family":"Uemura","sequence":"additional","affiliation":[{"name":"Department of Neurology Kyoto University Graduate School of Medicine, Kyoto, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hodaka","family":"Yamakado","sequence":"additional","affiliation":[{"name":"Department of Neurology Kyoto University Graduate School of Medicine, Kyoto, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryosuke","family":"Takahashi","sequence":"additional","affiliation":[{"name":"Department of Neurology Kyoto University Graduate School of Medicine, Kyoto, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2019,12,9]]},"reference":[{"key":"2020013108072772200_awz380-B1","doi-asserted-by":"crossref","first-page":"1568","DOI":"10.1007\/s00415-015-7742-3","article-title":"Prevalence and timeline of nonmotor symptoms in idiopathic rapid eye movement sleep behavior disorder","volume":"262","author":"Aguirre-Mardones","year":"2015","journal-title":"J Neurol"},{"key":"2020013108072772200_awz380-B2","doi-asserted-by":"crossref","first-page":"841","DOI":"10.1089\/10430340252899019","article-title":"Characterization of lentiviral vector-mediated gene transfer in adult mouse brain","volume":"13","author":"Baekelandt","year":"2002","journal-title":"Hum Gene Ther"},{"key":"2020013108072772200_awz380-B3","doi-asserted-by":"crossref","first-page":"560","DOI":"10.1111\/j.1471-4159.2008.05406.x","article-title":"Alpha-synuclein aggregation and cell death triggered by energy deprivation and dopamine overload are counteracted by D2\/D3 receptor activation","volume":"106","author":"Bellucci","year":"2008","journal-title":"J Neurochem"},{"key":"2020013108072772200_awz380-B4","doi-asserted-by":"crossref","first-page":"e27959","DOI":"10.1371\/journal.pone.0027959","article-title":"Redistribution of DAT\/\u03b1-synuclein complexes visualized by in situ proximity ligation assay in transgenic mice modeling early Parkinson\u2019s disease","volume":"6","author":"Bellucci","year":"2011","journal-title":"PLoS One"},{"key":"2020013108072772200_awz380-B5","doi-asserted-by":"crossref","first-page":"819","DOI":"10.1007\/s00401-017-1755-1","article-title":"Alpha-synuclein oligomers: a new hope","volume":"134","author":"Bengoa-Vergniory","year":"2017","journal-title":"Acta Neruopathol"},{"key":"2020013108072772200_awz380-B6","doi-asserted-by":"crossref","first-page":"1600","DOI":"10.1002\/mds.26431","article-title":"MDS research criteria for prodromal Parkinson\u2019s disease","volume":"30","author":"Berg","year":"2015","journal-title":"Mov Disord"},{"key":"2020013108072772200_awz380-B7","doi-asserted-by":"crossref","first-page":"509","DOI":"10.1007\/s12035-012-8330-5","article-title":"Alpha-synuclein posttranslational modification and alternative splicing as a trigger for neurodegeneration","volume":"47","author":"Beyer","year":"2013","journal-title":"Mol Neurobiol"},{"key":"2020013108072772200_awz380-B8","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1016\/j.sleep.2006.08.017","article-title":"Insights into REM sleep behavior disorder pathophysiology in brainstem- predominant Lewy body disease","volume":"8","author":"Boeve","year":"2007","journal-title":"Sleep Med"},{"key":"2020013108072772200_awz380-B9","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1002\/mds.26479","article-title":"Synaptic failure and \u03b1-synuclein","volume":"31","author":"Calo","year":"2016","journal-title":"Mov Disord"},{"key":"2020013108072772200_awz380-B10","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1016\/j.expneurol.2012.11.007","article-title":"Expression of human E46K-mutated alpha-synuclein in BAC-transgenic rats replicates early-stage Parkinson's disease features and enhances vulnerability to mitochondrial impairment","volume":"240","author":"Cannon","year":"2013","journal-title":"Exp Neurol"},{"key":"2020013108072772200_awz380-B11","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1016\/j.brainres.2011.01.064","article-title":"Decresed reuptake of dopamine in the dorsal striatum in the absence of \u03b1-synuclein","volume":"1382","author":"Chadchankar","year":"2011","journal-title":"Brain Res"},{"key":"2020013108072772200_awz380-B12","doi-asserted-by":"crossref","first-page":"1167","DOI":"10.1016\/S0140-6736(04)17103-1","article-title":"\u03b1-synuclein locus duplication as a cause of familial Parkinson's disease","volume":"364","author":"Chartier-Harlin","year":"2001","journal-title":"Lancet"},{"key":"2020013108072772200_awz380-B13","doi-asserted-by":"crossref","first-page":"715","DOI":"10.1002\/ana.21995","article-title":"Clinical progression in Parkinson disease and the neurobiology of axons","volume":"67","author":"Cheng","year":"2010","journal-title":"Ann Neurol"},{"key":"2020013108072772200_awz380-B14","doi-asserted-by":"crossref","first-page":"571","DOI":"10.1073\/pnas.97.2.571","article-title":"Acceleration of oligomerization, not fibrillization, is a shared property of both alpha-synuclein mutations linked to early-onset Parkinson\u2019s disease: implications for pathogenesis and therapy","volume":"97","author":"Conway","year":"2000","journal-title":"Proc Natl Acad Sci USA"},{"key":"2020013108072772200_awz380-B15","doi-asserted-by":"crossref","first-page":"3274","DOI":"10.1093\/hmg\/ddp265","article-title":"Expansion of the Parkinson disease-associated SNCA-Rep1 allele upregulates human alpha-synuclein in transgenic mouse brain","volume":"18","author":"Cronin","year":"2009","journal-title":"Hum Mol Genet"},{"key":"2020013108072772200_awz380-B16","doi-asserted-by":"crossref","first-page":"889","DOI":"10.1016\/S0896-6273(03)00568-3","article-title":"Parkinson's disease: mechanism and models","volume":"39","author":"Dauer","year":"2003","journal-title":"Neuron"},{"key":"2020013108072772200_awz380-B17","doi-asserted-by":"crossref","first-page":"342ra78","DOI":"10.1126\/scitranslmed.aaf3634","article-title":"\u03b1-Synuclein binds to TOM20 and inhibit mitochondrial protein import in Parkinson\u2019s disease","volume":"8","author":"Di Maio","year":"2016","journal-title":"Sci Transl Med"},{"key":"2020013108072772200_awz380-B18","doi-asserted-by":"crossref","first-page":"2283","DOI":"10.1093\/brain\/114.5.2283","article-title":"Ageing and Parkinson's disease: substantia nigra regional selectivity","volume":"114","author":"Fearnley","year":"1991","journal-title":"Brain"},{"key":"2020013108072772200_awz380-B19","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1111\/j.1460-9568.2008.06346.x","article-title":"Olfactory deficits in mice overexpressing human wildtype \u03b1-synuclein","volume":"28","author":"Fleming","year":"2008","journal-title":"Eur J Neurosci"},{"key":"2020013108072772200_awz380-B20","doi-asserted-by":"crossref","first-page":"351","DOI":"10.1002\/jnr.21125","article-title":"RNA interference-mediated knockdown of alpha-synuclein human dopaminergic neuroblastoma cells from MPP(+) toxicity and reduces dopamine transport","volume":"85","author":"Fountaine","year":"2007","journal-title":"J Neurosci Res"},{"key":"2020013108072772200_awz380-B21","doi-asserted-by":"crossref","first-page":"591","DOI":"10.1007\/s00429-011-0349-2","article-title":"A cytoarchitectonic and chemoarchitectonic analysis of the dopamine cell groups in the substantia nigra, ventral tegmental area, and retrorubral field in the mouse","volume":"217","author":"Fu","year":"2012","journal-title":"Brain Struct Funct"},{"key":"2020013108072772200_awz380-B22","doi-asserted-by":"crossref","first-page":"378","DOI":"10.1038\/nature20142","article-title":"Forward-genetics analysis of sleep in randomly mutagenized mice","volume":"539","author":"Funato","year":"2016","journal-title":"Nature"},{"key":"2020013108072772200_awz380-B23","doi-asserted-by":"crossref","first-page":"2120","DOI":"10.1093\/brain\/awt152","article-title":"The coeruleus\/subcoeruleus complex in rapid eye movement sleep behaviour disorders in Parkinson\u2019s disease","volume":"136","author":"Garc\u00eda-Lorenzo","year":"2013","journal-title":"Brain"},{"key":"2020013108072772200_awz380-B24","doi-asserted-by":"crossref","first-page":"521","DOI":"10.1016\/S0896-6273(02)00682-7","article-title":"Lee VM Neuronal alpha-synucleinopathy with severe movement disorder in mice expressing A53T human alpha-synuclein","volume":"34","author":"Giasson","year":"2002","journal-title":"Neuron"},{"key":"2020013108072772200_awz380-B25","doi-asserted-by":"crossref","first-page":"434","DOI":"10.1097\/WCO.0000000000000112","article-title":"Premotor and nonmotor features of Parkinson's disease","volume":"27","author":"Goldman","year":"2014","journal-title":"Curr Opin Neurol"},{"key":"2020013108072772200_awz380-B26","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1002\/ajmg.b.32288","article-title":"Alpha-synuclein (SNCA) polymorphisms and susceptibility to Parkinson's disease: a meta-analysis","volume":"168B","author":"Han","year":"2015","journal-title":"Am J Med Genet B Neuropsychiatr Genet"},{"key":"2020013108072772200_awz380-B27","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1016\/j.nbd.2013.04.017","article-title":"A novel alpha-synuclein-GFP mouse model displays progressive motor impairment, olfactory dysfunction and accumulation of alpha-synuclein-GFP","volume":"56","author":"Hansen","year":"2013","journal-title":"Neurobiol Dis"},{"key":"2020013108072772200_awz380-B28","doi-asserted-by":"crossref","first-page":"1169","DOI":"10.1016\/S0140-6736(04)17104-3","article-title":"Causal relation between \u03b1-synuclein gene duplication and familial Parkinson's disease","volume":"364","author":"Ib\u00e1\u00f1ez","year":"2004","journal-title":"Lancet"},{"key":"2020013108072772200_awz380-B29","doi-asserted-by":"crossref","first-page":"9008","DOI":"10.1038\/s41598-017-08720-5","article-title":"Cellular internalization of alpha-synuclein aggregates by cell surface heparan sulfate depends on aggregate conformation and cell type","volume":"7","author":"Ihse","year":"2017","journal-title":"Sci Rep"},{"key":"2020013108072772200_awz380-B30","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1007\/978-3-642-68970-3_9","article-title":"Revised Pathophysiology on BBB Damage: The Edema as an ingeniously Provided Condition for Cell Motility and Lesion Repair","volume":"8","author":"Ikuta","year":"1983","journal-title":"Acta Neuropathol Suppl"},{"key":"2020013108072772200_awz380-B31","doi-asserted-by":"crossref","first-page":"E4016","DOI":"10.1073\/pnas.1309143110","article-title":"Deficits in dopaminergic transmission precede neuron loss and dysfunction in a new Parkinson model","volume":"110","author":"Janezic","year":"2013","journal-title":"Proc Natl Acad Sci U S A"},{"key":"2020013108072772200_awz380-B32","doi-asserted-by":"crossref","first-page":"730","DOI":"10.1016\/j.bbadis.2008.07.006","article-title":"A critical evaluation of current staging of alpha-synuclein pathology in Lewy body disorders","volume":"1792","author":"Jellinger","year":"2009","journal-title":"Biochim Biophys Acta"},{"key":"2020013108072772200_awz380-B33","doi-asserted-by":"crossref","first-page":"2780","DOI":"10.1523\/JNEUROSCI.22-07-02780.2002","article-title":"Parkinson-like neurodegeneration induced by targeted overexpression of alpha-synuclein in the nigrostriatal system","volume":"22","author":"Kirik","year":"2002","journal-title":"J Neurosci"},{"key":"2020013108072772200_awz380-B34","doi-asserted-by":"crossref","first-page":"503","DOI":"10.1038\/nature06281","article-title":"Innate versus learned odour processing in the mouse olfactory bulb","volume":"450","author":"Kobayakawa","year":"2007","journal-title":"Nature"},{"key":"2020013108072772200_awz380-B35","first-page":"S1","article-title":"Autosomal dominant Parkinson's disease caused by SNCA duplications","volume":"1","author":"Konno","year":"2016","journal-title":"Parkisonism Relat Disord"},{"key":"2020013108072772200_awz380-B36","doi-asserted-by":"crossref","first-page":"1633","DOI":"10.1093\/hmg\/ddq038","article-title":"Extensive enteric nervous system abnormalities in mice transgenic for artificial chromosomes containing Parkinson disease-associated alpha-synuclein gene mutations precede central nervous system changes","volume":"19","author":"Kuo","year":"2010","journal-title":"Hum Mol Genet"},{"key":"2020013108072772200_awz380-B37","doi-asserted-by":"crossref","first-page":"1044","DOI":"10.1056\/NEJM199810083391506","article-title":"Parkinson's disease. First of two parts","volume":"339","author":"Lang","year":"1998","journal-title":"N Engl J Med"},{"key":"2020013108072772200_awz380-B38","doi-asserted-by":"crossref","first-page":"949","DOI":"10.1126\/science.1227157","article-title":"Pathological \u03b1-synuclein transmission initiates Parkinson-like neurodegeneration in nontransgenic mice","volume":"338","author":"Luk","year":"2012","journal-title":"Science"},{"key":"2020013108072772200_awz380-B39","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1016\/j.jneumeth.2015.11.009","article-title":"High-content analysis of \u03b1-synuclein aggregation and cell death in a cellular model of Parkinson's disease","volume":"261","author":"Macchi","year":"2016","journal-title":"J Neurosci Methods"},{"key":"2020013108072772200_awz380-B40","doi-asserted-by":"crossref","first-page":"23024","DOI":"10.1074\/jbc.M112.367011","article-title":"Exercise is more effective than diet control in preventing high fat diet-induced \u03b2-amyloid deposition and memory deficit in amyloid precursor protein transgenic mice","volume":"287","author":"Maesako","year":"2012","journal-title":"J Biol Chem"},{"key":"2020013108072772200_awz380-B41","doi-asserted-by":"crossref","first-page":"661","DOI":"10.1001\/jama.296.6.661","article-title":"Collaborative analysis of alpha-synuclein gene promoter variability and Parkinson disease","volume":"296","author":"Maraganore","year":"2006","journal-title":"JAMA"},{"key":"2020013108072772200_awz380-B42","doi-asserted-by":"crossref","first-page":"440","DOI":"10.1111\/j.1471-4159.2011.07576.x","article-title":"\u03b1-Synuclein oligomers oppose long-term potentiation and impair memory through a calcineurin-dependent mechanism: relevance to human synucleopathic diseases","volume":"120","author":"Martin","year":"2012","journal-title":"J Neurochem"},{"key":"2020013108072772200_awz380-B43","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s40478-014-0088-8","article-title":"Pathological alpha-synuclein propagates through neural networks","volume":"2","author":"Masuda-Suzukake","year":"2014","journal-title":"Acta Neuropathol Commun"},{"key":"2020013108072772200_awz380-B44","doi-asserted-by":"crossref","first-page":"1128","DOI":"10.1093\/brain\/awt037","article-title":"Prion-like spreading of pathological \u03b1-synuclein in brain","volume":"136","author":"Masuda-Suzukake","year":"2013","journal-title":"Brain"},{"key":"2020013108072772200_awz380-B45","doi-asserted-by":"crossref","first-page":"531","DOI":"10.3233\/JPD-140374","article-title":"Sleep dysfunction and EEG alterations in mice overexpressing alpha-synuclein","volume":"4","author":"McDowll","year":"2014","journal-title":"J Parkinsons Dis"},{"key":"2020013108072772200_awz380-B46","doi-asserted-by":"crossref","first-page":"1560","DOI":"10.1038\/nn.4641","article-title":"Dopamine induces soluble \u03b1-synuclein oligomers and nigrostriatal degeneration","volume":"20","author":"Mor","year":"2017","journal-title":"Nat Neurosci"},{"key":"2020013108072772200_awz380-B47","doi-asserted-by":"crossref","first-page":"412","DOI":"10.1093\/brain\/aws358","article-title":"A progressive dopaminergic phenotype associated with neurotoxic conversion of alpha-synuclein in BAC-transgenic rats","volume":"136","author":"Nuber","year":"2013","journal-title":"Brain"},{"key":"2020013108072772200_awz380-B48","doi-asserted-by":"crossref","first-page":"981","DOI":"10.1016\/j.parkreldis.2015.06.005","article-title":"Early-onset parkinsonism caused by alpha-synuclein gene triplication: clinical and genetic findings in a novel family","volume":"21","author":"Olgiati","year":"2015","journal-title":"Parkinsonism Relat Disord"},{"key":"2020013108072772200_awz380-B49","doi-asserted-by":"crossref","first-page":"3362","DOI":"10.1007\/s11064-017-2382-x","article-title":"The oligomer hypothesis in \u03b1-synucleinopathy","volume":"42","author":"Ono","year":"2017","journal-title":"Neurochem Res"},{"key":"2020013108072772200_awz380-B50","doi-asserted-by":"crossref","first-page":"e1867","DOI":"10.1371\/journal.pone.0001867","article-title":"Formation of toxic oligomeric alpha-synuclein species in living cells","volume":"3","author":"Outeiro","year":"2008","journal-title":"PLoS One"},{"key":"2020013108072772200_awz380-B51","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1016\/j.tins.2014.02.009","article-title":"Breakdown in REM sleep circuitry underlies REM sleep behaveor disorder","volume":"37","author":"Peever","year":"2014","journal-title":"Trends Neurosci"},{"key":"2020013108072772200_awz380-B52","doi-asserted-by":"crossref","first-page":"40699","DOI":"10.1038\/srep40699","article-title":"DOPAL derived alpha-synuclein oligomers impair synaptic vesicles physiological function","volume":"7","author":"Plotegher","year":"2017","journal-title":"Sci Rep"},{"key":"2020013108072772200_awz380-B53","doi-asserted-by":"crossref","first-page":"17013","DOI":"10.1038\/nrdp.2017.13","article-title":"Parkinson disease","volume":"3","author":"Poewe","year":"2017","journal-title":"Nat Rev Dis Primers"},{"key":"2020013108072772200_awz380-B54","doi-asserted-by":"crossref","first-page":"617","DOI":"10.1002\/mds.24996","article-title":"Identifying prodromal Parkinson's disease: pre-motor disorders in Parkinson's disease","volume":"27","author":"Postuma","year":"2012","journal-title":"Mov Disord"},{"key":"2020013108072772200_awz380-B56","doi-asserted-by":"crossref","first-page":"1496","DOI":"10.1093\/brain\/awu057","article-title":"Accumulation of oligomer-prone \u03b1-synuclein exacerbates synaptic and neuronal degenerateon","volume":"137","author":"Rockenstein","year":"2014","journal-title":"Brain"},{"key":"2020013108072772200_awz380-B57","doi-asserted-by":"crossref","first-page":"486","DOI":"10.1038\/nature15368","article-title":"Structure of the toxic core of \u03b1-synuclein from invisible crystals","volume":"525","author":"Rodriguez","year":"2015","journal-title":"Nature"},{"key":"2020013108072772200_awz380-B58","doi-asserted-by":"crossref","first-page":"215","DOI":"10.3233\/JPD-120130","article-title":"Neuronal expression of familial Parkinson\u2019s disease A53T \u03b1-synuclein causes early motor impairment, reduced anxiety and potential sleep disturbances in mice","volume":"3","author":"Rothman","year":"2013","journal-title":"J Parkinsons Dis"},{"key":"2020013108072772200_awz380-B59","doi-asserted-by":"crossref","first-page":"1303","DOI":"10.1038\/ng.485","article-title":"Genome-wide association study identifies common variants at four loci as genetic risk factors for Parkinson's disease","volume":"41","author":"Satake","year":"2009","journal-title":"Nat Genet"},{"key":"2020013108072772200_awz380-B60","doi-asserted-by":"crossref","first-page":"435","DOI":"10.1038\/nrn.2017.62","article-title":"Non-motor features of Parkinson disease","volume":"18","author":"Schapira","year":"2017","journal-title":"Nat Rev Neurosci"},{"key":"2020013108072772200_awz380-B61","doi-asserted-by":"crossref","first-page":"583","DOI":"10.1016\/S0896-6273(03)00024-2","article-title":"The formation of highly soluble oligomers of alpha-synuclein is regulated by fatty acids and enhanced in Parkinson\u2019s disease","volume":"37","author":"Sharon","year":"2003","journal-title":"Neuron"},{"key":"2020013108072772200_awz380-B62","doi-asserted-by":"crossref","DOI":"10.1073\/pnas.95.11.6469","article-title":"\u03b1-Synuclein in filamentous inclusions of Lewy bodies from Parkinson's disease and dementia with Lewy bodies","author":"Spillantini","year":"1998","journal-title":"Proc Natl Acad Sci"},{"key":"2020013108072772200_awz380-B63","doi-asserted-by":"crossref","first-page":"839","DOI":"10.1038\/42166","article-title":"Alpha-synuclein in Lewy bodies","volume":"388","author":"Spillantini","year":"1997","journal-title":"Nature"},{"key":"2020013108072772200_awz380-B64","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1002\/ana.67","article-title":"Clinical and pathological features of a Parkinsonian syndrome in a family with an Ala53Thr alpha-synuclein mutation","volume":"49","author":"Spira","year":"2001","journal-title":"Ann Neurol"},{"key":"2020013108072772200_awz380-B65","doi-asserted-by":"crossref","first-page":"296","DOI":"10.1007\/PL00007441","article-title":"C-terminal alpha-synuclein immunoreactivity in structures other than Lewy bodies in neurodegenerative disorders","volume":"99","author":"Takeda","year":"2000","journal-title":"Acta Neuropathol"},{"key":"2020013108072772200_awz380-B66","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1007\/s00401-010-0676-z","article-title":"Proteinase K-resistant \u03b1-synuclein is deposited in presynapses in human Lewy body disease and A53T \u03b1-synuclein transgenic mice","volume":"120","author":"Tanji","year":"2010","journal-title":"Acta Neuropathol"},{"key":"2020013108072772200_awz380-B67","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1016\/j.nbd.2013.10.005","article-title":"Region-specific deficits in dopamine, but not norepinephrine, signaling in a novel A30P alpha-synuclein BAC transgenic mouse","volume":"62","author":"Taylor","year":"2014","journal-title":"Neurobiol Dis"},{"key":"2020013108072772200_awz380-B68","doi-asserted-by":"crossref","first-page":"2054","DOI":"10.1016\/j.celrep.2014.05.033","article-title":"A-Synuclein immunotherapy blocks uptake and templated propagation of misfolded \u03b1-synuclein and neurodegeneration","volume":"7","author":"Tran","year":"2014","journal-title":"Cell Rep"},{"key":"2020013108072772200_awz380-B69","doi-asserted-by":"crossref","first-page":"8093","DOI":"10.1073\/pnas.110078997","article-title":"Nonapoptotic neurodegeneration in a transgenic mouse model of Huntington's disease","volume":"97","author":"Turmaine","year":"2000","journal-title":"Proc Natl Acad Sci U S A"},{"key":"2020013108072772200_awz380-B70","doi-asserted-by":"crossref","first-page":"709","DOI":"10.1212\/WNL.45.4.709","article-title":"Incidental Lewy body disease in a patient with REM sleep behavior disorder","volume":"45","author":"Uchiyama","year":"1995","journal-title":"Neurology"},{"key":"2020013108072772200_awz380-B71","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1186\/s13024-018-0257-5","article-title":"Inoculation of \u03b1-synuclein preformed fibrils into the mouse gastrointestinal tract induces Lewy body-like aggregates in the brainstem via the vagus nerve","volume":"13","author":"Uemura","year":"2018","journal-title":"Mol Neurodegener"},{"key":"2020013108072772200_awz380-B72","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1016\/j.nbd.2015.04.009","article-title":"Generation and characterization of novel conformation-specific monoclonal antibodies for \u03b1-synuclein pathology","volume":"79","author":"Vaikath","year":"2015","journal-title":"Neurobiol Dis"},{"key":"2020013108072772200_awz380-B73","doi-asserted-by":"crossref","first-page":"504","DOI":"10.1038\/s41467-017-02761-0","article-title":"Ventromedial medulla inhibitory neuron inactiveation induces REM sleep without atonia and REM sleep behavior disorder","volume":"9","author":"Valencia Garcia","year":"2018","journal-title":"Nat Commun"},{"key":"2020013108072772200_awz380-B74","doi-asserted-by":"crossref","first-page":"414","DOI":"10.1093\/brain\/aww310","article-title":"Genetic inactiveation of glutamate neurons in the rat subletrodorsal tegmental nucleus recapitulates REM sleep behavior disorder","volume":"140","author":"Valencia Garcia","year":"2017","journal-title":"Brain"},{"key":"2020013108072772200_awz380-B75","doi-asserted-by":"crossref","first-page":"750","DOI":"10.1016\/j.tins.2016.09.003","article-title":"\u03b1-Synuclein-based animal models of Parkinson's disease: challenges and opportunities in a new era","volume":"39","author":"Visanji","year":"2016","journal-title":"Trends Neurosci"},{"key":"2020013108072772200_awz380-B76","doi-asserted-by":"crossref","first-page":"e38545","DOI":"10.1371\/journal.pone.0038545","article-title":"The role of alpha-synuclein oligomerization and aggregation in cellular and animal models of Parkinson's disease","volume":"7","author":"Wan","year":"2012","journal-title":"PloS One"},{"key":"2020013108072772200_awz380-B78","doi-asserted-by":"crossref","first-page":"4194","DOI":"10.1073\/pnas.1100976108","article-title":"In vivo demonstration that \u03b1-synuclein oligomers are toxic","volume":"108","author":"Winner","year":"2011","journal-title":"Proc Natl Acad Sci USA"},{"key":"2020013108072772200_awz380-B79","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1016\/j.neures.2012.03.010","article-title":"\u03b1-Synuclein BAC transgenic mice as a model for Parkinson's disease manifested decreased anxiety-like behavior and hyperlocomotion","volume":"73","author":"Yamakado","year":"2012","journal-title":"Neurosci Res"},{"key":"2020013108072772200_awz380-B80","doi-asserted-by":"crossref","first-page":"e0119928","DOI":"10.1371\/journal.pone.0119928","article-title":"Olfactory dysfunction and neurotransmitter disturbance in olfactory bulb of transgenic mice expressing human A53T mutant alpha-synuclein","volume":"10","author":"Zhang","year":"2015","journal-title":"PLoS One"}],"container-title":["Brain"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/academic.oup.com\/brain\/article-pdf\/143\/1\/249\/32298668\/awz380.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"http:\/\/academic.oup.com\/brain\/article-pdf\/143\/1\/249\/32298668\/awz380.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2020,1,31]],"date-time":"2020-01-31T08:08:40Z","timestamp":1580458120000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/brain\/article\/143\/1\/249\/5663565"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,12,9]]},"references-count":78,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2019,12,9]]},"published-print":{"date-parts":[[2020,1,1]]}},"URL":"https:\/\/doi.org\/10.1093\/brain\/awz380","relation":{},"ISSN":["0006-8950","1460-2156"],"issn-type":[{"value":"0006-8950","type":"print"},{"value":"1460-2156","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2020,1]]},"published":{"date-parts":[[2019,12,9]]}}}