{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,31]],"date-time":"2026-10-31T17:23:44Z","timestamp":1793467424959,"version":"4.5.0"},"reference-count":48,"publisher":"Public Library of Science (PLoS)","issue":"11","license":[{"start":{"date-parts":[[2016,11,8]],"date-time":"2016-11-08T00:00:00Z","timestamp":1478563200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000065","name":"National Institute of Neurological Disorders and Stroke","doi-asserted-by":"publisher","award":["NS053912, NS 073415 and NS061257"],"award-info":[{"award-number":["NS053912, NS 073415 and NS061257"]}],"id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000265","name":"Medical Research Council","doi-asserted-by":"publisher","award":["MRC G1002272"],"award-info":[{"award-number":["MRC G1002272"]}],"id":[{"id":"10.13039\/501100000265","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000864","name":"Michael J. Fox Foundation for Parkinson's Research","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000864","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"DOI":"10.1371\/journal.pone.0165964","type":"journal-article","created":{"date-parts":[[2016,11,8]],"date-time":"2016-11-08T18:36:49Z","timestamp":1478630209000},"page":"e0165964","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":67,"title":["Bifunctional Anti-Non-Amyloid Component \u03b1-Synuclein Nanobodies Are Protective In Situ"],"prefix":"10.1371","volume":"11","author":[{"given":"David C.","family":"Butler","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shubhada N.","family":"Joshi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erwin De","family":"Genst","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ankit S.","family":"Baghel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher M.","family":"Dobson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne","family":"Messer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2016,11,8]]},"reference":[{"issue":"Suppl 2","key":"ref1","doi-asserted-by":"crossref","first-page":"S2","DOI":"10.1212\/WNL.51.2_Suppl_2.S2","article-title":"Biochemical aspects of Parkinson&apos;s disease","volume":"51","author":"O Hornykiewicz","year":"1998","journal-title":"Neurology"},{"issue":"3","key":"ref2","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1097\/00005072-199603000-00001","article-title":"Neuropathology of Parkinson&apos;s disease","volume":"55","author":"LS Forno","year":"1996","journal-title":"Journal of neuropathology and experimental neurology"},{"issue":"6","key":"ref3","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1038\/sj.mp.4000446","article-title":"Alpha synuclein is present in Lewy bodies in sporadic Parkinson&apos;s disease","volume":"3","author":"E Mezey","year":"1998","journal-title":"Molecular psychiatry"},{"issue":"6645","key":"ref4","doi-asserted-by":"crossref","first-page":"839","DOI":"10.1038\/42166","article-title":"Alpha-synuclein in Lewy bodies","volume":"388","author":"MG Spillantini","year":"1997","journal-title":"Nature"},{"issue":"4","key":"ref5","doi-asserted-by":"crossref","first-page":"2380","DOI":"10.1074\/jbc.M008919200","article-title":"A hydrophobic stretch of 12 amino acid residues in the middle of alpha-synuclein is essential for filament assembly","volume":"276","author":"BI Giasson","year":"2001","journal-title":"The Journal of biological chemistry"},{"issue":"12","key":"ref6","doi-asserted-by":"crossref","first-page":"3338","DOI":"10.1523\/JNEUROSCI.0285-07.2007","article-title":"Aggregated alpha-synuclein mediates dopaminergic neurotoxicity in vivo","volume":"27","author":"M Periquet","year":"2007","journal-title":"The Journal of neuroscience: the official journal of the Society for Neuroscience"},{"issue":"1","key":"ref7","doi-asserted-by":"crossref","first-page":"136","DOI":"10.1016\/j.jmb.2007.11.096","article-title":"An scFv intrabody against the nonamyloid component of alpha-synuclein reduces intracellular aggregation and toxicity","volume":"377","author":"SM Lynch","year":"2008","journal-title":"Journal of molecular biology"},{"issue":"3","key":"ref8","doi-asserted-by":"crossref","first-page":"447","DOI":"10.1007\/s13311-013-0193-6","article-title":"Intrabodies as neuroprotective therapeutics","volume":"10","author":"A Messer","year":"2013","journal-title":"Neurotherapeutics"},{"issue":"43","key":"ref9","doi-asserted-by":"crossref","first-page":"13589","DOI":"10.1523\/JNEUROSCI.4286-09.2009","article-title":"Intrabody gene therapy ameliorates motor, cognitive, and neuropathological symptoms in multiple mouse models of Huntington&apos;s disease","volume":"29","author":"AL Southwell","year":"2009","journal-title":"The Journal of neuroscience: the official journal of the Society for Neuroscience"},{"issue":"11","key":"ref10","doi-asserted-by":"crossref","first-page":"1907","DOI":"10.1016\/j.bbapap.2014.08.016","article-title":"Antibodies and protein misfolding: From structural research tools to therapeutic strategies","volume":"1844","author":"E De Genst","year":"2014","journal-title":"Biochim Biophys Acta"},{"issue":"2","key":"ref11","doi-asserted-by":"crossref","first-page":"1002","DOI":"10.1073\/pnas.022631799","article-title":"Effects of intracellular expression of anti-huntingtin antibodies of various specificities on mutant huntingtin aggregation and toxicity","volume":"99","author":"A Khoshnan","year":"2002","journal-title":"Proceedings of the National Academy of Sciences of the United States of America"},{"issue":"8","key":"ref12","doi-asserted-by":"crossref","first-page":"4764","DOI":"10.1073\/pnas.071058398","article-title":"Human single-chain Fv intrabodies counteract in situ huntingtin aggregation in cellular models of Huntington&apos;s disease","volume":"98","author":"JM Lecerf","year":"2001","journal-title":"Proceedings of the National Academy of Sciences of the United States of America"},{"issue":"12","key":"ref13","doi-asserted-by":"crossref","first-page":"e29199","DOI":"10.1371\/journal.pone.0029199","article-title":"Bifunctional anti-huntingtin proteasome-directed intrabodies mediate efficient degradation of mutant huntingtin exon 1 protein fragments","volume":"6","author":"DC Butler","year":"2011","journal-title":"PloS one"},{"issue":"6","key":"ref14","doi-asserted-by":"crossref","first-page":"686","DOI":"10.4161\/mabs.21696","article-title":"Fusion to a highly charged proteasomal retargeting sequence increases soluble cytoplasmic expression and efficacy of diverse anti-synuclein intrabodies","volume":"4","author":"SN Joshi","year":"2012","journal-title":"mAbs"},{"issue":"34","key":"ref15","doi-asserted-by":"crossref","first-page":"12486","DOI":"10.1073\/pnas.1402012111","article-title":"Tumorigenicity of hypoxic respiring cancer cells revealed by a hypoxia\u2013cell cycle dual reporter","volume":"111","author":"A Le","year":"2014","journal-title":"Proceedings of the National Academy of Sciences of the United States of America"},{"issue":"52","key":"ref16","doi-asserted-by":"crossref","first-page":"34970","DOI":"10.1074\/jbc.273.52.34970","article-title":"Generation of destabilized green fluorescent protein as a transcription reporter","volume":"273","author":"X Li","year":"1998","journal-title":"The Journal of biological chemistry"},{"key":"ref17","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1016\/S0076-6879(99)02006-6","article-title":"Comparison of enhanced green fluorescent protein and its destabilized form as transcription reporters","volume":"302","author":"X Zhao","year":"1999","journal-title":"Methods Enzymol"},{"key":"ref18","article-title":"Immunotherapeutic Approaches Targeting Amyloid-beta, alpha-Synuclein, and Tau for the Treatment of Neurodegenerative Disorders","author":"E Valera","year":"2015","journal-title":"Neurotherapeutics: the journal of the American Society for Experimental NeuroTherapeutics"},{"issue":"14","key":"ref19","doi-asserted-by":"crossref","first-page":"2397","DOI":"10.1016\/j.jmb.2013.01.040","article-title":"Nanobodies raised against monomeric alpha-synuclein distinguish between fibrils at different maturation stages","volume":"425","author":"T Guilliams","year":"2013","journal-title":"Journal of molecular biology"},{"issue":"12","key":"ref20","doi-asserted-by":"crossref","first-page":"6763","DOI":"10.1073\/pnas.100110097","article-title":"The Huntington&apos;s disease protein interacts with p53 and CREB-binding protein and represses transcription","volume":"97","author":"JS Steffan","year":"2000","journal-title":"Proceedings of the National Academy of Sciences of the United States of America"},{"issue":"8","key":"ref21","doi-asserted-by":"crossref","first-page":"597","DOI":"10.1038\/nmeth901","article-title":"An improved mRFP1 adds red to bimolecular fluorescence complementation","volume":"3","author":"G Jach","year":"2006","journal-title":"Nat Methods"},{"issue":"2","key":"ref22","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1006\/exnr.2000.7551","article-title":"ST14A cells have properties of a medium-size spiny neuron","volume":"167","author":"ME Ehrlich","year":"2001","journal-title":"Experimental neurology"},{"issue":"5","key":"ref23","doi-asserted-by":"crossref","first-page":"e5727","DOI":"10.1371\/journal.pone.0005727","article-title":"Conformational targeting of fibrillar polyglutamine proteins in live cells escalates aggregation and cytotoxicity","volume":"4","author":"E Kvam","year":"2009","journal-title":"PloS one"},{"issue":"3","key":"ref24","doi-asserted-by":"crossref","first-page":"1634","DOI":"10.3390\/biom5031634","article-title":"Toxic Oligomeric Alpha-Synuclein Variants Present in Human Parkinson&apos;s Disease Brains Are Differentially Generated in Mammalian Cell Models","volume":"5","author":"W Xin","year":"2015","journal-title":"Biomolecules"},{"issue":"1","key":"ref25","doi-asserted-by":"crossref","first-page":"363","DOI":"10.1038\/nprot.2006.55","article-title":"In vitro measurement of cell death with the annexin A5 affinity assay","volume":"1","author":"H van Genderen","year":"2006","journal-title":"Nature protocols"},{"issue":"3","key":"ref26","doi-asserted-by":"crossref","first-page":"901","DOI":"10.1016\/S0306-4522(01)00113-0","article-title":"Alpha-synuclein-enhanced green fluorescent protein fusion proteins form proteasome sensitive inclusions in primary neurons","volume":"104","author":"PJ McLean","year":"2001","journal-title":"Neuroscience"},{"issue":"2\u20133","key":"ref27","doi-asserted-by":"crossref","first-page":"195","DOI":"10.3109\/08830189309061696","article-title":"Medical applications of single-chain antibodies","volume":"10","author":"JS Huston","year":"1993","journal-title":"Int Rev Immunol"},{"issue":"4","key":"ref28","doi-asserted-by":"crossref","first-page":"489","DOI":"10.1111\/jnc.13575","article-title":"Walking the tightrope: proteostasis and neurodegenerative disease","volume":"137","author":"JJ Yerbury","year":"2016","journal-title":"Journal of neurochemistry"},{"issue":"Pt 3","key":"ref29","doi-asserted-by":"crossref","first-page":"577","DOI":"10.1042\/bj3460577","article-title":"Alpha-synuclein overexpression promotes aggregation of mutant huntingtin","volume":"346","author":"RA Furlong","year":"2000","journal-title":"The Biochemical journal"},{"issue":"3","key":"ref30","doi-asserted-by":"crossref","first-page":"485","DOI":"10.1093\/hmg\/ddr477","article-title":"alpha-Synuclein levels modulate Huntington&apos;s disease in mice","volume":"21","author":"S Corrochano","year":"2012","journal-title":"Human molecular genetics"},{"issue":"3","key":"ref31","doi-asserted-by":"crossref","first-page":"495","DOI":"10.1093\/hmg\/ddr507","article-title":"alpha-Synuclein accumulates in huntingtin inclusions but forms independent filaments and its deficiency attenuates early phenotype in a mouse model of Huntington&apos;s disease","volume":"21","author":"C Tomas-Zapico","year":"2012","journal-title":"Human molecular genetics"},{"issue":"7","key":"ref32","doi-asserted-by":"crossref","first-page":"1898","DOI":"10.1093\/hmg\/ddu606","article-title":"alpha-Synuclein modifies mutant huntingtin aggregation and neurotoxicity in Drosophila","volume":"24","author":"GM Pocas","year":"2015","journal-title":"Human molecular genetics"},{"issue":"3","key":"ref33","doi-asserted-by":"crossref","first-page":"431","DOI":"10.4161\/auto.19259","article-title":"alpha-Synuclein levels affect autophagosome numbers in vivo and modulate Huntington disease pathology","volume":"8","author":"S Corrochano","year":"2012","journal-title":"Autophagy"},{"issue":"11","key":"ref34","doi-asserted-by":"crossref","first-page":"678","DOI":"10.1007\/s00109-003-0464-5","article-title":"Protein aggregation and aggregate toxicity: new insights into protein folding, misfolding diseases and biological evolution","volume":"81","author":"M Stefani","year":"2003","journal-title":"J Mol Med (Berl)"},{"issue":"4","key":"ref35","first-page":"277","article-title":"Single domain camel antibodies: current status","volume":"74","author":"S Muyldermans","year":"2001","journal-title":"J Biotechnol"},{"issue":"3","key":"ref36","doi-asserted-by":"crossref","first-page":"521","DOI":"10.1016\/S0014-5793(97)01062-4","article-title":"Selection and identification of single domain antibody fragments from camel heavy-chain antibodies","volume":"414","author":"M Arbabi Ghahroudi","year":"1997","journal-title":"FEBS letters"},{"issue":"6","key":"ref37","doi-asserted-by":"crossref","first-page":"489","DOI":"10.1093\/protein\/gzq022","article-title":"Physico-chemical determinants of soluble intrabody expression in mammalian cell cytoplasm","volume":"23","author":"E Kvam","year":"2010","journal-title":"Protein engineering, design & selection: PEDS"},{"issue":"4","key":"ref38","doi-asserted-by":"crossref","first-page":"e19338","DOI":"10.1371\/journal.pone.0019338","article-title":"Passive immunization reduces behavioral and neuropathological deficits in an alpha-synuclein transgenic model of Lewy body disease","volume":"6","author":"E Masliah","year":"2011","journal-title":"PloS one"},{"issue":"2","key":"ref39","doi-asserted-by":"crossref","first-page":"326","DOI":"10.1016\/j.jmb.2010.07.001","article-title":"Structure and properties of a complex of alpha-synuclein and a single-domain camelid antibody","volume":"402","author":"EJ De Genst","year":"2010","journal-title":"Journal of molecular biology"},{"key":"ref40","article-title":"Structural effects of two camelid nanobodies directed to distinct C-terminal epitopes on alpha-synuclein","author":"F El-Turk","year":"2016","journal-title":"Biochemistry"},{"key":"ref41","doi-asserted-by":"crossref","first-page":"606172","DOI":"10.1155\/2012\/606172","article-title":"The Aggregation of Huntingtin and alpha-Synuclein","volume":"2012","author":"ME Chanez-Cardenas","year":"2012","journal-title":"J Biophys"},{"issue":"3","key":"ref42","doi-asserted-by":"crossref","first-page":"846","DOI":"10.1111\/j.1471-4159.2007.05032.x","article-title":"Sensitive biochemical aggregate detection reveals aggregation onset before symptom development in cellular and murine models of Huntington&apos;s disease","volume":"104","author":"A Weiss","year":"2008","journal-title":"Journal of neurochemistry"},{"issue":"16","key":"ref43","doi-asserted-by":"crossref","first-page":"2443","DOI":"10.1097\/00001756-200411150-00001","article-title":"Can autophagy protect against neurodegeneration caused by aggregate-prone proteins?","volume":"15","author":"B Ravikumar","year":"2004","journal-title":"Neuroreport"},{"issue":"6","key":"ref44","doi-asserted-by":"crossref","first-page":"1023","DOI":"10.1083\/jcb.201003122","article-title":"alpha-Synuclein impairs macroautophagy: implications for Parkinson&apos;s disease","volume":"190","author":"AR Winslow","year":"2010","journal-title":"J Cell Biol"},{"issue":"2","key":"ref45","doi-asserted-by":"crossref","first-page":"685","DOI":"10.1007\/s12035-014-8738-1","article-title":"Overexpression of human E46K mutant alpha-synuclein impairs macroautophagy via inactivation of JNK1-Bcl-2 pathway","volume":"50","author":"JQ Yan","year":"2014","journal-title":"Molecular neurobiology"},{"issue":"2","key":"ref46","doi-asserted-by":"crossref","first-page":"435","DOI":"10.3390\/biom5020435","article-title":"The Interplay between Alpha-Synuclein Clearance and Spreading","volume":"5","author":"T Lopes da Fonseca","year":"2015","journal-title":"Biomolecules"},{"key":"ref47","article-title":"Nanoscopic insights into seeding mechanisms and toxicity of alpha-synuclein species in neurons","author":"D Pinotsi","year":"2016","journal-title":"Proceedings of the National Academy of Sciences of the United States of America"},{"key":"ref48","doi-asserted-by":"crossref","first-page":"1023","DOI":"10.1016\/j.ymthe.2004.08.019","article-title":"A human single-chain Fv intrabody blocks aberrant cellular effects of overexpressed alpha-synuclein","volume":"10","author":"C Zhou","year":"2004","journal-title":"Mol Ther"}],"container-title":["PLOS ONE"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/dx.plos.org\/10.1371\/journal.pone.0165964","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,6,20]],"date-time":"2024-06-20T12:50:47Z","timestamp":1718887847000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0165964"}},"subtitle":[],"editor":[{"given":"Stephan N.","family":"Witt","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2016,11,8]]},"references-count":48,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2016,11,8]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0165964","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,11,8]]}}}