{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T02:44:29Z","timestamp":1791254669631,"version":"4.1.0"},"reference-count":25,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2014,8,11]],"date-time":"2014-08-11T00:00:00Z","timestamp":1407715200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/3.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Movement Disorders"],"published-print":{"date-parts":[[2014,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>Alpha\u2010synuclein (\u03b1\u2010Syn) aggregates are the main component of Lewy bodies, which are the characteristic pathological feature in Parkinson's disease (PD) brain. Evidence that \u03b1\u2010Syn aggregation can be propagated between neurones has led to the suggestion that this mechanism is responsible for the stepwise progression of PD pathology. Decreasing \u03b1\u2010Syn expression is predicted to attenuate this process and is thus an attractive approach to delay or halt PD progression. We have used \u03b1\u2010Syn small interfering RNA (siRNA) to reduce total and aggregated \u03b1\u2010Syn levels in mouse brains. To achieve widespread delivery of siRNAs to the brain we have peripherally injected modified exosomes expressing Ravies virus glycoprotein loaded with siRNA. Normal mice were analyzed 3 or 7 days after injection. To evaluate whether this approach can decrease \u03b1\u2010Syn aggregates, we repeated the treatment using transgenic mice expressing the human phosphorylation\u2010mimic S129D \u03b1\u2010Syn, which exhibits aggregation. In normal mice we detected significantly reduced \u03b1\u2010Syn messenger RNA (mRNA) and protein levels throughout the brain 3 and 7 days after treatment with RVG\u2010exosomes loaded with siRNA to \u03b1\u2010Syn. In S129D \u03b1\u2010Syn transgenic mice we found a decreased \u03b1\u2010Syn mRNA and protein levels throughout the brain 7 days after injection. This resulted in significant reductions in intraneuronal protein aggregates, including in dopaminergic neurones of the substantia nigra. This study highlights the therapeutic potential of RVG\u2010exosome delivery of siRNA to delay and reverse brain \u03b1\u2010Syn pathological conditions. \u00a9 2014 The Authors. <jats:italic>Movement<\/jats:italic> Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.<\/jats:p>","DOI":"10.1002\/mds.25978","type":"journal-article","created":{"date-parts":[[2014,8,11]],"date-time":"2014-08-11T10:11:45Z","timestamp":1407751905000},"page":"1476-1485","source":"Crossref","is-referenced-by-count":486,"title":["Systemic exosomal siRNA delivery reduced alpha\u2010synuclein aggregates in brains of transgenic mice"],"prefix":"10.1002","volume":"29","author":[{"given":"J. Mark","family":"Cooper","sequence":"first","affiliation":[{"name":"Department of Clinical Neuroscience, Institute of Neurology University College London London United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P.B. Oscar","family":"Wiklander","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine Karolinska Institutet Huddinge Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joel Z.","family":"Nordin","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine Karolinska Institutet Huddinge Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raya","family":"Al\u2010Shawi","sequence":"additional","affiliation":[{"name":"Centre for Biomedical Science, Division of Medicine UCL London United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew J.","family":"Wood","sequence":"additional","affiliation":[{"name":"Department of Physiology, Anatomy and Genetics University of Oxford Oxford United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mansi","family":"Vithlani","sequence":"additional","affiliation":[{"name":"Department of Clinical Neuroscience, Institute of Neurology University College London London United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anthony H. V.","family":"Schapira","sequence":"additional","affiliation":[{"name":"Department of Clinical Neuroscience, Institute of Neurology University College London London United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J. Paul","family":"Simons","sequence":"additional","affiliation":[{"name":"Centre for Biomedical Science, Division of Medicine UCL London United Kingdom"},{"name":"Wolfson Drug Discovery Unit, Centre for Amyloidosis and Acute Phase Proteins UCL London United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samir","family":"El\u2010Andaloussi","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine Karolinska Institutet Huddinge Sweden"},{"name":"Department of Physiology, Anatomy and Genetics University of Oxford Oxford United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lydia","family":"Alvarez\u2010Erviti","sequence":"additional","affiliation":[{"name":"Department of Clinical Neuroscience, Institute of Neurology University College London London United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2014,8,11]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2006.09.026"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0197-4580(02)00065-9"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbadis.2008.07.006"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1186\/1750-1326-3-19"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0167-7799(97)01095-0"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a009431"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11095-008-9815-9"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/nbt.1807"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncb1596"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/cddis.2013.73"},{"key":"e_1_2_7_12_1","first-page":"872","article-title":"Phosphorylation does not prompt, nor prevent, the formation of \u03b1\u2010Syn toxic species in a rat model of Parkinson's disease","volume":"18","author":"Azeredo da Silveira S","year":"2009","journal-title":"Hum Mol Genet"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M600933200"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.3080-04.2004"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1090278"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(04)17103-1"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.2617-07.2007"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0896-6273(00)80886-7"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1227157"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.24066"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2010.04.034"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncb748"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncb748"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbd.2013.03.014"},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)80623-6"},{"key":"e_1_2_7_26_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0708285104"}],"container-title":["Movement Disorders"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fmds.25978","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/movementdisorders.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/mds.25978","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,20]],"date-time":"2025-10-20T11:26:40Z","timestamp":1760959600000},"score":1,"resource":{"primary":{"URL":"https:\/\/movementdisorders.onlinelibrary.wiley.com\/doi\/10.1002\/mds.25978"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2014,8,11]]},"references-count":25,"journal-issue":{"issue":"12","published-print":{"date-parts":[[2014,10]]}},"alternative-id":["10.1002\/mds.25978"],"URL":"https:\/\/doi.org\/10.1002\/mds.25978","archive":["Portico"],"relation":{},"ISSN":["0885-3185","1531-8257"],"issn-type":[{"value":"0885-3185","type":"print"},{"value":"1531-8257","type":"electronic"}],"subject":[],"published":{"date-parts":[[2014,8,11]]}}}