{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T03:03:56Z","timestamp":1791947036870,"version":"4.3.4"},"reference-count":82,"publisher":"National Academy of Sciences","issue":"12","license":[{"start":{"date-parts":[[2020,9,9]],"date-time":"2020-09-09T00:00:00Z","timestamp":1599609600000},"content-version":"vor","delay-in-days":184,"URL":"https:\/\/www.pnas.org\/site\/aboutpnas\/licenses.xhtml"}],"funder":[{"name":"EU-FP7 MC-ITN IN-SENS","award":["60671"],"award-info":[{"award-number":["60671"]}]},{"name":"Research Commission of the Medical Faculty of the University of D\u00fcsseldorf","award":["9772651"],"award-info":[{"award-number":["9772651"]}]},{"name":"Bundesministerium f\u00fcr Bildung und Forschung REMOVAGE","award":["01GQ1422A"],"award-info":[{"award-number":["01GQ1422A"]}]}],"content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2020,3,24]]},"abstract":"<jats:title>Significance<\/jats:title>\n                  <jats:p>Synucleinopathies such as Parkinson\u2019s disease feature deposition of misfolded \u03b1-synuclein. It is likely that cellular proteostasis compensates for misfolded \u03b1-synuclein to some extent, but, once exhausted, \u03b1-synuclein can form seeds for a prion-like spread in the brain. Here, we demonstrate that, in human dopaminergic neurons and in mouse brain, H1N1 influenza virus induces aggregation of \u03b1-synuclein by blocking protein degradation pathways. Following intranasal instillation, H1N1 spreading along the olfactory route into brain areas mimics \u03b1-synuclein deposits in synucleinopathies. H1N1 may therefore be considered a risk factor for synucleinopathies that could potentially be minimized by regular vaccination. On the contrary, H1N1 tropism for olfactory epithelium suggests that live attenuated virus vaccines should be investigated for possible long-term effects on protein misfolding.<\/jats:p>","DOI":"10.1073\/pnas.1906466117","type":"journal-article","created":{"date-parts":[[2020,3,9]],"date-time":"2020-03-09T20:25:23Z","timestamp":1583785523000},"page":"6741-6751","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":137,"title":["Disruption of cellular proteostasis by H1N1 influenza A virus causes \u03b1-synuclein aggregation"],"prefix":"10.1073","volume":"117","author":[{"given":"Rita","family":"Marreiros","sequence":"first","affiliation":[{"name":"Department Neuropathology, Heinrich Heine University D\u00fcsseldorf Medical School, 40225 D\u00fcsseldorf, Germany;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreas","family":"M\u00fcller-Schiffmann","sequence":"additional","affiliation":[{"name":"Department Neuropathology, Heinrich Heine University D\u00fcsseldorf Medical School, 40225 D\u00fcsseldorf, Germany;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Svenja V.","family":"Trossbach","sequence":"additional","affiliation":[{"name":"Department Neuropathology, Heinrich Heine University D\u00fcsseldorf Medical School, 40225 D\u00fcsseldorf, Germany;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4330-7187","authenticated-orcid":false,"given":"Ingrid","family":"Prikulis","sequence":"additional","affiliation":[{"name":"Department Neuropathology, Heinrich Heine University D\u00fcsseldorf Medical School, 40225 D\u00fcsseldorf, Germany;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sebastian","family":"H\u00e4nsch","sequence":"additional","affiliation":[{"name":"Center for Advanced Imaging, Heinrich Heine University D\u00fcsseldorf, 40225 D\u00fcsseldorf, Germany;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefanie","family":"Weidtkamp-Peters","sequence":"additional","affiliation":[{"name":"Center for Advanced Imaging, Heinrich Heine University D\u00fcsseldorf, 40225 D\u00fcsseldorf, Germany;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana Raquel","family":"Moreira","sequence":"additional","affiliation":[{"name":"Prosetta Biosciences, San Francisco, CA 94107"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shriya","family":"Sahu","sequence":"additional","affiliation":[{"name":"Prosetta Biosciences, San Francisco, CA 94107"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Irina","family":"Soloviev","sequence":"additional","affiliation":[{"name":"Prosetta Biosciences, San Francisco, CA 94107"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suganya","family":"Selvarajah","sequence":"additional","affiliation":[{"name":"Prosetta Biosciences, San Francisco, CA 94107"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vishwanath R.","family":"Lingappa","sequence":"additional","affiliation":[{"name":"Prosetta Biosciences, San Francisco, CA 94107"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carsten","family":"Korth","sequence":"additional","affiliation":[{"name":"Department Neuropathology, Heinrich Heine University D\u00fcsseldorf Medical School, 40225 D\u00fcsseldorf, Germany;"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2020,3,9]]},"reference":[{"key":"e_1_3_3_1_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1067122"},{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM200105173442006"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.95.11.6469"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20160368"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41380-018-0133-2"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.5389-07.2008"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1038\/mp.2015.194"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0903691106"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a024588"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1098\/rsob.160328"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20112457"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-019-02057-1"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.aac4354"},{"key":"e_1_3_3_14_2","first-page":"a034090","article-title":"Proteostasis in viral infection: Unfolding the complex virus-chaperone interplay","author":"Aviner R.","year":"2019","unstructured":"R. Aviner, J. Frydman, Proteostasis in viral infection: Unfolding the complex virus-chaperone interplay. Cold Spring Harb. Perspect. Biol., a034090 (2019).","journal-title":"Cold Spring Harb. Perspect. Biol."},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.01623-05"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1210198110"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.28652"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrmicro.2016.60"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.virusres.2014.10.003"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1136\/bmjopen-2018-024687"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/cix412"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/cis454"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1089\/088282403322396208"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0900096106"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.00239-11"},{"key":"e_1_3_3_26_2","doi-asserted-by":"publisher","DOI":"10.1002\/path.4461"},{"key":"e_1_3_3_27_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.00417-11"},{"key":"e_1_3_3_28_2","doi-asserted-by":"publisher","DOI":"10.1111\/irv.12079"},{"key":"e_1_3_3_29_2","doi-asserted-by":"publisher","DOI":"10.1093\/jnen\/60.7.696"},{"key":"e_1_3_3_30_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1111179108"},{"key":"e_1_3_3_31_2","doi-asserted-by":"publisher","DOI":"10.1002\/mds.22908"},{"key":"e_1_3_3_32_2","doi-asserted-by":"publisher","DOI":"10.3109\/00207454.2012.760560"},{"key":"e_1_3_3_33_2","doi-asserted-by":"publisher","DOI":"10.1002\/mds.25077"},{"key":"e_1_3_3_34_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1750-2659.2011.00232.x"},{"key":"e_1_3_3_35_2","doi-asserted-by":"publisher","DOI":"10.3201\/eid2405.180075"},{"key":"e_1_3_3_36_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bj.2019.01.004"},{"key":"e_1_3_3_37_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(00)78541-2"},{"key":"e_1_3_3_38_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1521463112"},{"key":"e_1_3_3_39_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainresbull.2005.11.022"},{"key":"e_1_3_3_40_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M205518200"},{"key":"e_1_3_3_41_2","doi-asserted-by":"publisher","DOI":"10.1099\/00221287-5-1-46"},{"key":"e_1_3_3_42_2","doi-asserted-by":"publisher","DOI":"10.1002\/ana.25446"},{"key":"e_1_3_3_43_2","doi-asserted-by":"publisher","DOI":"10.1038\/305245a0"},{"key":"e_1_3_3_44_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopsych.2011.03.027"},{"key":"e_1_3_3_45_2","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/dds111"},{"key":"e_1_3_3_46_2","doi-asserted-by":"publisher","DOI":"10.1007\/978-981-10-8456-0_5"},{"key":"e_1_3_3_47_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.42.3.640"},{"key":"e_1_3_3_48_2","unstructured":"Roche Laboratories Tamiflu (oseltamivir phosphate) information NDA 21-087\/S-033 NDA 21-246\/S-021. https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/label\/2006\/021087s033ppi.pdf. Assessed 19 February 2020."},{"key":"e_1_3_3_49_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.chom.2009.09.005"},{"key":"e_1_3_3_50_2","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2018.03120"},{"key":"e_1_3_3_51_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.5809-11.2012"},{"key":"e_1_3_3_52_2","doi-asserted-by":"publisher","DOI":"10.4161\/auto.4451"},{"key":"e_1_3_3_53_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M113.457408"},{"key":"e_1_3_3_54_2","doi-asserted-by":"publisher","DOI":"10.1038\/emm.2013.45"},{"key":"e_1_3_3_55_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41374-019-0195-z"},{"key":"e_1_3_3_56_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.23-01-00297.2003"},{"key":"e_1_3_3_57_2","doi-asserted-by":"publisher","DOI":"10.1038\/ncb1328"},{"key":"e_1_3_3_58_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1101738"},{"key":"e_1_3_3_59_2","doi-asserted-by":"publisher","DOI":"10.1111\/jnc.14704"},{"key":"e_1_3_3_60_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(04)17103-1"},{"key":"e_1_3_3_61_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.3545-12.2012"},{"key":"e_1_3_3_62_2","doi-asserted-by":"publisher","DOI":"10.1155\/2012\/736905"},{"key":"e_1_3_3_63_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pbio.0030156"},{"key":"e_1_3_3_64_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrmicro865"},{"key":"e_1_3_3_65_2","doi-asserted-by":"publisher","DOI":"10.4161\/auto.6685"},{"key":"e_1_3_3_66_2","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/dds018"},{"key":"e_1_3_3_67_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajpath.2012.06.033"},{"key":"e_1_3_3_68_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M115.712083"},{"key":"e_1_3_3_69_2","first-page":"1263","article-title":"Differential roles of the ubiquitin proteasome system and autophagy in the clearance of soluble and aggregated TDP-43 species","volume":"127","author":"Scotter E. L.","year":"2014","unstructured":"E. L. Scotter ., Differential roles of the ubiquitin proteasome system and autophagy in the clearance of soluble and aggregated TDP-43 species. J. Cell Sci. 127, 1263\u20131278 (2014).","journal-title":"J. Cell Sci."},{"key":"e_1_3_3_70_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature05853"},{"key":"e_1_3_3_71_2","doi-asserted-by":"publisher","DOI":"10.2353\/ajpath.2007.070188"},{"key":"e_1_3_3_72_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2009.01.021"},{"key":"e_1_3_3_73_2","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/11.9.1107"},{"key":"e_1_3_3_74_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2017.06.021"},{"key":"e_1_3_3_75_2","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms9938"},{"key":"e_1_3_3_76_2","doi-asserted-by":"publisher","DOI":"10.1016\/0361-9230(84)90148-5"},{"key":"e_1_3_3_77_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.181.6.2161"},{"key":"e_1_3_3_78_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00441-017-2733-6"},{"key":"e_1_3_3_79_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0197-4580(02)00065-9"},{"key":"e_1_3_3_80_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-009-0537-9"},{"key":"e_1_3_3_81_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2019.05.035"},{"key":"e_1_3_3_82_2","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2019.00351"}],"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/www.pnas.org\/syndication\/doi\/10.1073\/pnas.1906466117","content-type":"unspecified","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.1906466117","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,4,13]],"date-time":"2022-04-13T05:06:47Z","timestamp":1649826407000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/full\/10.1073\/pnas.1906466117"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,3,9]]},"references-count":82,"journal-issue":{"issue":"12","published-print":{"date-parts":[[2020,3,24]]}},"alternative-id":["10.1073\/pnas.1906466117"],"URL":"https:\/\/doi.org\/10.1073\/pnas.1906466117","relation":{"has-review":[{"id-type":"doi","id":"10.3410\/f.737530012.793587857","asserted-by":"object"}]},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,3,9]]},"assertion":[{"value":"2020-03-09","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}