{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,24]],"date-time":"2026-07-24T01:13:00Z","timestamp":1784855580440,"version":"3.55.0"},"reference-count":116,"publisher":"Portland Press Ltd.","issue":"5","license":[{"start":{"date-parts":[[2022,9,16]],"date-time":"2022-09-16T00:00:00Z","timestamp":1663286400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["portlandpress.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2022,10,31]]},"abstract":"<jats:p>Parkinson's disease (PD) is a common neurodegenerative condition affecting a significant number of individuals globally, resulting in the presentation of debilitating motor and non-motor symptoms, including bradykinesia, resting tremor, as well as mood and sleep disorders. The pathology of PD has been observed to spread through the central nervous system resulting in progressive brain degeneration and a poor prognosis. Aggregated forms of the protein \u03b1-synuclein, particularly intermediary aggregates, referred to as oligomers, or preformed fibrils, have been implicated as the causative agent in the degeneration of neuronal processes, including the dysfunction of axonal transport, mitochondrial activity, and ultimately cellular death. Extracellular vesicles (EVs) have been strongly implicated in the propagation of PD pathology. Current observations suggest that aggregated \u03b1-synuclein is transported between neurons via small EVs in a series of exocytosis and endocytosis cellular processes leading to the observed spread of neurotoxicity and cellular death. Despite some understanding of the role of EVs in neurodegeneration, the exact mechanism by which these lipidic particles participate in the progression of Parkinson's pathology is not entirely understood. Here we review the current understanding of the role of EVs in the propagation of PD and explore their potential as a therapeutic target.<\/jats:p>","DOI":"10.1042\/bst20220204","type":"journal-article","created":{"date-parts":[[2022,9,16]],"date-time":"2022-09-16T11:49:59Z","timestamp":1663328999000},"page":"1303-1314","update-policy":"https:\/\/doi.org\/10.1042\/crossmark_policy","source":"Crossref","is-referenced-by-count":26,"title":["Propagation of Parkinson's disease by extracellular vesicle production and secretion"],"prefix":"10.1042","volume":"50","author":[{"given":"Laura E.","family":"Shippey","sequence":"first","affiliation":[{"name":"1Department of Biosciences and Chemistry, Sheffield Hallam University, Sheffield, U.K."},{"name":"2Department of Biochemistry and Chemistry, La Trobe Institute for Molecular Science, La Trobe University, Bundoora, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6740-1445","authenticated-orcid":false,"given":"Susan G.","family":"Campbell","sequence":"additional","affiliation":[{"name":"1Department of Biosciences and Chemistry, Sheffield Hallam University, Sheffield, U.K."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5581-2354","authenticated-orcid":false,"given":"Andrew F.","family":"Hill","sequence":"additional","affiliation":[{"name":"2Department of Biochemistry and Chemistry, La Trobe Institute for Molecular Science, La Trobe University, Bundoora, Australia"},{"name":"3Institute for Health and Sport, Victoria University, Footscray, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David P.","family":"Smith","sequence":"additional","affiliation":[{"name":"1Department of Biosciences and Chemistry, Sheffield Hallam University, Sheffield, U.K."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"288","published-online":{"date-parts":[[2022,9,16]]},"reference":[{"key":"2022103115571361000_BST-2022-0204CC1","doi-asserted-by":"publisher","first-page":"776847","DOI":"10.3389\/fpubh.2021.77684","article-title":"Global trends in the incidence, prevalence, and years lived with disability of Parkinson's disease in 204 countries\/territories from 1990 to 2019","volume":"9","year":"2021","journal-title":"Front. Public Health"},{"key":"2022103115571361000_BST-2022-0204CC2","first-page":"504","article-title":"Philip","volume":"40","year":"2015","journal-title":"P&T (Lawrenceville, N.J.)"},{"key":"2022103115571361000_BST-2022-0204CC3","doi-asserted-by":"publisher","first-page":"552","DOI":"10.3389\/fnins.2019.00552","article-title":"Prion-like mechanisms in Parkinson's disease","volume":"13","year":"2019","journal-title":"Front. Neurosci."},{"key":"2022103115571361000_BST-2022-0204CC4","doi-asserted-by":"publisher","first-page":"727","DOI":"10.1016\/j.neubiorev.2016.07.010","article-title":"Motor symptoms in Parkinson's disease: a unified framework","volume":"68","year":"2016","journal-title":"Neurosci. Biobehav. Rev."},{"key":"2022103115571361000_BST-2022-0204CC5","doi-asserted-by":"publisher","first-page":"119","DOI":"10.1016\/j.parkreldis.2015.09.004","article-title":"Non-motor symptoms in Parkinson's disease","volume":"22","year":"2016","journal-title":"Park. Relat. Disord."},{"key":"2022103115571361000_BST-2022-0204CC6","doi-asserted-by":"publisher","first-page":"14","DOI":"10.1111\/j.1468-1331.2008.02056.x","article-title":"Non-motor symptoms in Parkinson's disease","volume":"15","year":"2008","journal-title":"Eur. J. Neurol."},{"key":"2022103115571361000_BST-2022-0204CC7","doi-asserted-by":"publisher","first-page":"211","DOI":"10.1159\/000506742","article-title":"Clinical features and risk factors of Parkinson's disease in a population of Khyber Pakhtunkhwa, Pakistan: a case-control study","volume":"19","year":"2020","journal-title":"Neuro-Degener. Dis."},{"key":"2022103115571361000_BST-2022-0204CC8","doi-asserted-by":"publisher","first-page":"393","DOI":"10.7861\/clinmed.2020-0220","article-title":"Update on the diagnosis and management of Parkinson's disease","volume":"20","year":"2020","journal-title":"Clin. Med. (Lond.)"},{"key":"2022103115571361000_BST-2022-0204CC9","doi-asserted-by":"publisher","first-page":"1239","DOI":"10.2174\/1570159X15666170510143821","article-title":"Levodopa in Parkinson's disease: current status and future developments","volume":"16","year":"2018","journal-title":"Curr. Neuropharmacol."},{"key":"2022103115571361000_BST-2022-0204CC10","doi-asserted-by":"publisher","first-page":"190","DOI":"10.4103\/aian.AIAN_239_17","article-title":"Levodopa-induced dyskinesia: clinical features, pathophysiology, and medical management","volume":"20","year":"2017","journal-title":"Ann. Indian Acad. Neurol."},{"key":"2022103115571361000_BST-2022-0204CC11","volume-title":"Levodopa (L-Dopa). StatPearls Treasure Island (FL)","year":"2022"},{"key":"2022103115571361000_BST-2022-0204CC12","doi-asserted-by":"publisher","first-page":"302","DOI":"10.1016\/j.neuroscience.2018.03.026","article-title":"Phosphorylated \u03b1-synuclein accumulations and Lewy body-like pathology distributed in Parkinson's disease-related brain areas of aged rhesus monkeys treated with MPTP","volume":"379","year":"2018","journal-title":"Neuroscience"},{"key":"2022103115571361000_BST-2022-0204CC13","doi-asserted-by":"publisher","first-page":"4971","DOI":"10.1073\/pnas.1913904117","article-title":"The process of Lewy body formation, rather than simply \u03b1-synuclein fibrillization, is one of the major drivers of neurodegeneration","volume":"117","year":"2020","journal-title":"Proc. Natl Acad. Sci. U.S.A."},{"key":"2022103115571361000_BST-2022-0204CC14","doi-asserted-by":"publisher","first-page":"461","DOI":"10.3233\/JPD-130230","article-title":"The role of oxidative stress in Parkinson's disease","volume":"3","year":"2013","journal-title":"J. Parkinson's Dis."},{"key":"2022103115571361000_BST-2022-0204CC15","doi-asserted-by":"publisher","first-page":"130","DOI":"10.1038\/nm.3457","article-title":"Cell-to-cell transmission of pathogenic proteins in neurodegenerative diseases","volume":"20","year":"2014","journal-title":"Nat. Med."},{"key":"2022103115571361000_BST-2022-0204CC16","doi-asserted-by":"publisher","first-page":"1539","DOI":"10.1007\/s10571-018-0622-5","article-title":"Secretion and uptake of \u03b1-synuclein via extracellular vesicles in cultured cells","volume":"38","year":"2018","journal-title":"Cell Mol. Neurobiol."},{"key":"2022103115571361000_BST-2022-0204CC17","doi-asserted-by":"publisher","first-page":"9269","DOI":"10.1523\/JNEUROSCI.0147-18.2019","article-title":"Extracellular vesicles and neurodegenerative diseases","volume":"39","year":"2019","journal-title":"J. Neurosci."},{"key":"2022103115571361000_BST-2022-0204CC18","doi-asserted-by":"publisher","first-page":"e2011196118","DOI":"10.1073\/pnas.2011196118","article-title":"Mechanistic basis for receptor-mediated pathological \u03b1-synuclein fibril cell-to-cell transmission in Parkinson's disease","volume":"118","year":"2021","journal-title":"Proc. Natl Acad. Sci. U.S.A."},{"key":"2022103115571361000_BST-2022-0204CC19","doi-asserted-by":"publisher","first-page":"27066","DOI":"10.3402\/jev.v4.27066","article-title":"Biological properties of extracellular vesicles and their physiological functions","volume":"4","year":"2015","journal-title":"J. Extracell. Vesicles"},{"key":"2022103115571361000_BST-2022-0204CC20","doi-asserted-by":"publisher","first-page":"143","DOI":"10.1007\/978-1-0716-0759-6_10","article-title":"Extracellular vesicles and their roles in cancer progression","volume":"2174","year":"2021","journal-title":"Methods Mol. Biol."},{"key":"2022103115571361000_BST-2022-0204CC21","doi-asserted-by":"publisher","first-page":"875376","DOI":"10.3389\/fcell.2022.875376","article-title":"Extracellular vesicles in cardiovascular diseases: diagnosis and therapy","volume":"10","year":"2022","journal-title":"Front. Cell Dev. Biol."},{"key":"2022103115571361000_BST-2022-0204CC22","doi-asserted-by":"publisher","first-page":"727","DOI":"10.3390\/cells8070727","article-title":"Overview of extracellular vesicles, their origin, composition, purpose, and methods for exosome isolation and analysis","volume":"8","year":"2019","journal-title":"Cells"},{"key":"2022103115571361000_BST-2022-0204CC23","doi-asserted-by":"publisher","first-page":"1535750","DOI":"10.1080\/20013078.2018.1535750","article-title":"Minimal information for studies of extracellular vesicles 2018 (MISEV2018): a position statement of the international society for extracellular vesicles and update of the MISEV2014 guidelines","volume":"7","year":"2018","journal-title":"J. Extracell. Vesicles"},{"key":"2022103115571361000_BST-2022-0204CC24","doi-asserted-by":"publisher","first-page":"1141","DOI":"10.3390\/cells9051141","article-title":"The role of extracellular vesicles in the hallmarks of cancer and drug resistance","volume":"9","year":"2020","journal-title":"Cells"},{"key":"2022103115571361000_BST-2022-0204CC25","doi-asserted-by":"publisher","first-page":"399","DOI":"10.1096\/fba.2020-00127","article-title":"The ins and outs of microvesicles","volume":"3","year":"2021","journal-title":"FASEB Bioadv."},{"key":"2022103115571361000_BST-2022-0204CC26","doi-asserted-by":"publisher","first-page":"135","DOI":"10.1080\/19336918.2016.1236899","article-title":"Mechanisms and functions of extracellular vesicle release in vivo\u2014what we can learn from flies and worms","volume":"11","year":"2016","journal-title":"Cell Adhes. Migr."},{"key":"2022103115571361000_BST-2022-0204CC27","doi-asserted-by":"publisher","first-page":"e1001604","DOI":"10.1371\/journal.pbio.1001604","article-title":"Neurotransmitter-triggered transfer of exosomes mediates oligodendrocyte-neuron communication","volume":"11","year":"2013","journal-title":"PLoS Biol."},{"key":"2022103115571361000_BST-2022-0204CC28","doi-asserted-by":"publisher","first-page":"7105","DOI":"10.1074\/jbc.M112.410944","article-title":"Neuronal exosomal miRNA-dependent translational regulation of astroglial glutamate transporter GLT1","volume":"288","year":"2013","journal-title":"J. Biol. Chem."},{"key":"2022103115571361000_BST-2022-0204CC29","doi-asserted-by":"publisher","first-page":"1789326","DOI":"10.1080\/20013078.2020.1789326","article-title":"Cargo and cell-specific differences in extracellular vesicle populations identified by multiplexed immunofluorescent analysis","volume":"9","year":"2020","journal-title":"J. Extracell. Vesicles"},{"key":"2022103115571361000_BST-2022-0204CC30","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1038\/s41598-017-01115-6","article-title":"Neurons export extracellular vesicles enriched in cysteine string protein and misfolded protein cargo","volume":"7","year":"2017","journal-title":"Sci. Rep."},{"key":"2022103115571361000_BST-2022-0204CC31","doi-asserted-by":"publisher","first-page":"580030","DOI":"10.3389\/fneur.2020.580030","article-title":"Insights into the proteomic profiling of extracellular vesicles for the identification of early biomarkers of neurodegeneration","volume":"11","year":"2020","journal-title":"Front. Neurol."},{"key":"2022103115571361000_BST-2022-0204CC32","doi-asserted-by":"publisher","first-page":"877","DOI":"10.1016\/j.bpj.2020.12.031","article-title":"Internalization of \u03b1-synuclein oligomers into SH-SY5Y cells","volume":"120","year":"2021","journal-title":"Biophys. J."},{"key":"2022103115571361000_BST-2022-0204CC33","doi-asserted-by":"publisher","first-page":"42","DOI":"10.1186\/1750-1326-7-42","article-title":"Exosomal cell-to-cell transmission of alpha synuclein oligomers","volume":"7","year":"2012","journal-title":"Mol. Neurodegener."},{"key":"2022103115571361000_BST-2022-0204CC34","doi-asserted-by":"publisher","first-page":"337","DOI":"10.1016\/j.neures.2010.12.020","article-title":"Alpha-synuclein release by neurons activates the inflammatory response in a microglial cell line","volume":"69","year":"2011","journal-title":"Neurosci. Res."},{"key":"2022103115571361000_BST-2022-0204CC35","doi-asserted-by":"publisher","first-page":"9262","DOI":"10.1074\/jbc.M109.081125","article-title":"Direct transfer of \u03b1-synuclein from neuron to astroglia causes inflammatory responses in synucleinopathies","volume":"285","year":"2010","journal-title":"J. Biol. Chem."},{"key":"2022103115571361000_BST-2022-0204CC36","doi-asserted-by":"publisher","first-page":"173","DOI":"10.3390\/ijms17020173","article-title":"Focus on extracellular vesicles: exosomes and their role in protein trafficking and biomarker potential in Alzheimer's and Parkinson's disease","volume":"17","year":"2016","journal-title":"Int. J. Mol. Sci."},{"key":"2022103115571361000_BST-2022-0204CC37","doi-asserted-by":"publisher","first-page":"1663","DOI":"10.1126\/science.1195227","article-title":"\u03b1-Synuclein promotes SNARE-complex assembly in vivo and in vitro","volume":"329","year":"2010","journal-title":"Science"},{"key":"2022103115571361000_BST-2022-0204CC38","doi-asserted-by":"publisher","first-page":"66","DOI":"10.1016\/j.neuron.2009.12.023","article-title":"Increased expression of alpha-synuclein reduces neurotransmitter release by inhibiting synaptic vesicle reclustering after endocytosis","volume":"65","year":"2010","journal-title":"Neuron"},{"key":"2022103115571361000_BST-2022-0204CC39","doi-asserted-by":"publisher","first-page":"2279","DOI":"10.1016\/j.bpj.2010.07.056","article-title":"Effects of curvature and composition on \u03b1-synuclein binding to lipid vesicles","volume":"99","year":"2010","journal-title":"Biophys. J."},{"key":"2022103115571361000_BST-2022-0204CC40","doi-asserted-by":"publisher","first-page":"702639","DOI":"10.3389\/fnagi.2021.702639","article-title":"Alpha-synuclein as a biomarker of Parkinson's disease: good, but not good enough","volume":"13","year":"2021","journal-title":"Front Aging Neurosci."},{"key":"2022103115571361000_BST-2022-0204CC41","doi-asserted-by":"publisher","first-page":"356","DOI":"10.3389\/fphar.2020.00356","article-title":"Modeling Parkinson's disease with the alpha-SYNUCLEIN protein","volume":"11","year":"2020","journal-title":"Front. Pharmacol."},{"key":"2022103115571361000_BST-2022-0204CC42","doi-asserted-by":"publisher","first-page":"727","DOI":"10.1038\/nrn1199","article-title":"The role of \u03b1-synuclein in Parkinson's disease: insights from animal models","volume":"4","year":"2003","journal-title":"Nat. Rev. Neurosci."},{"key":"2022103115571361000_BST-2022-0204CC43","doi-asserted-by":"publisher","first-page":"a009399","DOI":"10.1101\/cshperspect.a009399","article-title":"\u03b1-Synuclein in Parkinson's disease","volume":"2","year":"2012","journal-title":"Cold Spring Harb. Perspect. Med."},{"key":"2022103115571361000_BST-2022-0204CC44","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1038\/s42003-018-0242-0","article-title":"Alpha-synuclein stepwise aggregation reveals features of an early onset mutation in Parkinson's disease","volume":"2","year":"2019","journal-title":"Commun. Biol."},{"key":"2022103115571361000_BST-2022-0204CC45","doi-asserted-by":"publisher","first-page":"1089","DOI":"10.1016\/S0022-2836(02)00735-0","article-title":"\u03b1-Synuclein, especially the Parkinson's disease-associated mutants, forms pore-like annular and tubular protofibrils","volume":"322","year":"2002","journal-title":"J. Mol. Biol."},{"key":"2022103115571361000_BST-2022-0204CC46","doi-asserted-by":"publisher","first-page":"1378","DOI":"10.1038\/ng.3454","article-title":"Multisystem Lewy body disease and the other parkinsonian disorders","volume":"47","year":"2015","journal-title":"Nat. Genet."},{"key":"2022103115571361000_BST-2022-0204CC47","doi-asserted-by":"publisher","first-page":"839","DOI":"10.1038\/42166","article-title":"[Alpha]-Synuclein in Lewy bodies","volume":"388","year":"1997","journal-title":"Nature (London)"},{"key":"2022103115571361000_BST-2022-0204CC48","doi-asserted-by":"publisher","first-page":"45","DOI":"10.1038\/nature16531","article-title":"Structural disorder of monomeric \u03b1-synuclein persists in mammalian cells","volume":"530","year":"2016","journal-title":"Nature"},{"key":"2022103115571361000_BST-2022-0204CC49","doi-asserted-by":"publisher","first-page":"4254","DOI":"10.1021\/jacs.6b05335","article-title":"Alpha-synuclein disease mutations are structurally defective and locally affect membrane binding","volume":"139","year":"2017","journal-title":"J. Am. Chem. Soc."},{"key":"2022103115571361000_BST-2022-0204CC50","doi-asserted-by":"publisher","first-page":"1814","DOI":"10.1038\/s41467-021-21937-3","article-title":"The release of toxic oligomers from \u03b1-synuclein fibrils induces dysfunction in neuronal cells","volume":"12","year":"2021","journal-title":"Nat. Commun."},{"key":"2022103115571361000_BST-2022-0204CC51","doi-asserted-by":"publisher","first-page":"E1994","DOI":"10.1073\/pnas.1421204112","article-title":"Structural characterization of toxic oligomers that are kinetically trapped during \u03b1-synuclein fibril formation","volume":"112","year":"2015","journal-title":"Proc. Natl Acad. Sci. U.S.A."},{"key":"2022103115571361000_BST-2022-0204CC52","doi-asserted-by":"publisher","first-page":"485","DOI":"10.1042\/BJ20150159","article-title":"Distinct higher-order \u03b1-synuclein oligomers induce intracellular aggregation","volume":"468","year":"2015  15","journal-title":"Biochem. J."},{"key":"2022103115571361000_BST-2022-0204CC53","doi-asserted-by":"publisher","first-page":"8645","DOI":"10.3390\/ijms21228645","article-title":"The role of \u03b1-synuclein oligomers in Parkinson's disease","volume":"21","year":"2020","journal-title":"Int. J. Mol. Sci."},{"key":"2022103115571361000_BST-2022-0204CC54","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1038\/s41467-018-03509-0","article-title":"A common mechanism of proteasome impairment by neurodegenerative disease-associated oligomers","volume":"9","year":"2018","journal-title":"Nat. Commun."},{"key":"2022103115571361000_BST-2022-0204CC55","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1038\/s41467-018-04422-2","article-title":"\u03b1-synuclein oligomers interact with ATP synthase and open the permeability transition pore in Parkinson's disease","volume":"9","year":"2018","journal-title":"Nat. Commun."},{"key":"2022103115571361000_BST-2022-0204CC56","doi-asserted-by":"publisher","first-page":"e14292","DOI":"10.1371\/journal.pone.0014292","article-title":"Membrane permeabilization by oligomeric \u03b1-synuclein: in search of the mechanism","volume":"5","year":"2010","journal-title":"PLoS One"},{"key":"2022103115571361000_BST-2022-0204CC57","doi-asserted-by":"publisher","first-page":"376","DOI":"10.1089\/ars.2015.6343","article-title":"Alpha-synuclein oligomers interact with metal ions to induce oxidative stress and neuronal death in Parkinson's disease","volume":"24","year":"2016","journal-title":"Antioxid. Redox Signal."},{"key":"2022103115571361000_BST-2022-0204CC58","doi-asserted-by":"publisher","first-page":"105312","DOI":"10.1016\/j.neuint.2022.105312","article-title":"Amyloid beta oligomers-induced parkin aggravates ER stress-mediated cell death through a positive feedback loop","volume":"155","year":"2022","journal-title":"Neurochem. Int."},{"key":"2022103115571361000_BST-2022-0204CC59","doi-asserted-by":"publisher","first-page":"dmm038042","DOI":"10.1242\/dmm.038042","article-title":"Recapitulating Parkinson's disease pathology in a three-dimensional human neural cell culture model","volume":"12","year":"2019","journal-title":"Dis. Model. Mech."},{"key":"2022103115571361000_BST-2022-0204CC60","doi-asserted-by":"publisher","first-page":"7671","DOI":"10.1073\/pnas.1315346111","article-title":"Solution conditions determine the relative importance of nucleation and growth processes in \u03b1-synuclein aggregation","volume":"111","year":"2014","journal-title":"Proc. Natl Acad. Sci. U.S.A."},{"key":"2022103115571361000_BST-2022-0204CC61","doi-asserted-by":"publisher","first-page":"781","DOI":"10.1016\/j.molcel.2015.07.012","article-title":"Human Hsp70 disaggregase reverses Parkinson's-linked \u03b1-synuclein amyloid fibrils","volume":"59","year":"2015","journal-title":"Mol. Cell"},{"key":"2022103115571361000_BST-2022-0204CC62","doi-asserted-by":"publisher","first-page":"24310","DOI":"10.1073\/pnas.1903268116","article-title":"Hsp110 mitigates \u03b1-synuclein pathology in vivo","volume":"116","year":"2019","journal-title":"Proc. Natl Acad. Sci. U.S.A."},{"key":"2022103115571361000_BST-2022-0204CC63","doi-asserted-by":"publisher","first-page":"41","DOI":"10.1016\/j.parkreldis.2021.06.010","article-title":"Preformed fibrils generated from mouse alpha-synuclein produce more inclusion pathology in rats than fibrils generated from rat alpha-synuclein","volume":"89","year":"2021","journal-title":"Park. Relat. Disord."},{"key":"2022103115571361000_BST-2022-0204CC64","doi-asserted-by":"publisher","first-page":"2135","DOI":"10.1038\/nprot.2014.143","article-title":"Addition of exogenous \u03b1-synuclein pre-formed fibrils to primary neuronal cultures to seed recruitment of endogenous \u03b1-synuclein to Lewy body and Lewy neurite-like aggregates","volume":"9","year":"2014","journal-title":"Nat. Protoc."},{"key":"2022103115571361000_BST-2022-0204CC65","doi-asserted-by":"publisher","first-page":"9808","DOI":"10.1523\/JNEUROSCI.1788-16.2017","article-title":"Prying into the prion hypothesis for Parkinson's disease","volume":"37","year":"2017","journal-title":"J. Neurosci."},{"key":"2022103115571361000_BST-2022-0204CC66","doi-asserted-by":"publisher","first-page":"9683","DOI":"10.1073\/pnas.0308413101","article-title":"Cells release prions in association with exosomes","volume":"101","year":"2004","journal-title":"Proc. Natl Acad. Sci. U.S.A."},{"key":"2022103115571361000_BST-2022-0204CC67","doi-asserted-by":"publisher","first-page":"1612","DOI":"10.1212\/CON.0000000000000251","article-title":"Prion diseases","volume":"21","year":"2015","journal-title":"Continuum (Minneap Minn)"},{"key":"2022103115571361000_BST-2022-0204CC68","doi-asserted-by":"publisher","first-page":"582","DOI":"10.1002\/path.2145","article-title":"Packaging of prions into exosomes is associated with a novel pathway of PrP processing","volume":"211","year":"2007","journal-title":"J. Pathol."},{"key":"2022103115571361000_BST-2022-0204CC69","doi-asserted-by":"publisher","first-page":"192","DOI":"10.1111\/j.1471-4159.2009.06324.x","article-title":"Seeding induced by alpha-synuclein oligomers provides evidence for spreading of alpha-synuclein pathology","volume":"111","year":"2009","journal-title":"J. Neurochem."},{"key":"2022103115571361000_BST-2022-0204CC70","doi-asserted-by":"publisher","first-page":"6838","DOI":"10.1523\/JNEUROSCI.5699-09.2010","article-title":"Cell-produced alpha-synuclein is secreted in a calcium-dependent manner by exosomes and impacts neuronal survival","volume":"30","year":"2010","journal-title":"J. Neurosci."},{"key":"2022103115571361000_BST-2022-0204CC71","doi-asserted-by":"publisher","first-page":"aah3374","DOI":"10.1126\/science.aah3374","article-title":"Pathological \u03b1-synuclein transmission initiated by binding lymphocyte-activation gene 3","volume":"353","year":"2016","journal-title":"Science"},{"key":"2022103115571361000_BST-2022-0204CC72","doi-asserted-by":"publisher","first-page":"2171","DOI":"10.4161\/auto.36436","article-title":"Autophagy modulates SNCA\/\u03b1-synuclein release, thereby generating a hostile microenvironment","volume":"10","year":"2015","journal-title":"Autophagy"},{"key":"2022103115571361000_BST-2022-0204CC73","doi-asserted-by":"publisher","first-page":"109099","DOI":"10.1016\/j.celrep.2021.109099","article-title":"\u03b1-Synuclein mutation impairs processing of endomembrane compartments and promotes exocytosis and seeding of \u03b1-synuclein pathology","volume":"35","year":"2021","journal-title":"Cell Rep."},{"key":"2022103115571361000_BST-2022-0204CC74","doi-asserted-by":"publisher","first-page":"2969","DOI":"10.1074\/jbc.M114.585703","article-title":"Acceleration of \u03b1-synuclein aggregation by exosomes","volume":"290","year":"2015","journal-title":"J. Biol. Chem."},{"key":"2022103115571361000_BST-2022-0204CC75","doi-asserted-by":"publisher","first-page":"695","DOI":"10.1007\/s00401-015-1408-1","article-title":"Extracellular vesicle sorting of \u03b1-Synuclein is regulated by sumoylation","volume":"129","year":"2015","journal-title":"Acta Neuropathol."},{"key":"2022103115571361000_BST-2022-0204CC76","doi-asserted-by":"publisher","first-page":"1249","DOI":"10.1152\/physrev.00008.2014","article-title":"Neuronal SUMOylation: mechanisms, physiology, and roles in neuronal dysfunction","volume":"94","year":"2014","journal-title":"Physiol. Rev."},{"key":"2022103115571361000_BST-2022-0204CC77","doi-asserted-by":"publisher","first-page":"13176","DOI":"10.1073\/pnas.1704351114","article-title":"SUMOylation and ubiquitination reciprocally regulate \u03b1-synuclein degradation and pathological aggregation","volume":"114","year":"2017","journal-title":"Proc. Natl Acad. Sci. U.S.A."},{"key":"2022103115571361000_BST-2022-0204CC78","doi-asserted-by":"publisher","first-page":"119","DOI":"10.1016\/j.neulet.2013.03.057","article-title":"Increased SUMO-1 expression in the unilateral rotenone-lesioned mouse model of Parkinson's disease","volume":"544","year":"2013","journal-title":"Neurosci. Lett."},{"key":"2022103115571361000_BST-2022-0204CC79","doi-asserted-by":"publisher","first-page":"683920","DOI":"10.1155\/2013\/683920","article-title":"Neuroprotective function of DJ-1 in Parkinson's disease","volume":"2013","year":"2013","journal-title":"Oxidative Med. Cell. Longev."},{"key":"2022103115571361000_BST-2022-0204CC80","doi-asserted-by":"publisher","first-page":"49","DOI":"10.1083\/jcb.201010117","article-title":"Sumoylation inhibits alpha-synuclein aggregation and toxicity","volume":"194","year":"2011","journal-title":"J. Cell Biol."},{"key":"2022103115571361000_BST-2022-0204CC81","doi-asserted-by":"publisher","first-page":"1763","DOI":"10.3390\/cells10071763","article-title":"Extracellular vesicles under oxidative stress conditions: biological properties and physiological roles","volume":"10","year":"2021","journal-title":"Cells"},{"key":"2022103115571361000_BST-2022-0204CC82","doi-asserted-by":"publisher","first-page":"236","DOI":"10.3389\/fnmol.2018.00236","article-title":"Oxidative stress in Parkinson's disease: a systematic review and meta-analysis","volume":"11","year":"2018","journal-title":"Front. Mol. Neurosci."},{"key":"2022103115571361000_BST-2022-0204CC83","doi-asserted-by":"publisher","first-page":"2203","DOI":"10.1016\/j.ymthe.2020.06.026","article-title":"Adiponectin stimulates exosome release to enhance mesenchymal stem-cell-driven therapy of heart failure in mice","volume":"28","year":"2020","journal-title":"Mol. Ther."},{"key":"2022103115571361000_BST-2022-0204CC84","doi-asserted-by":"publisher","first-page":"7559","DOI":"10.1007\/s11033-021-06733-y","article-title":"Impact of native and external factors on exosome release: understanding reactive exosome secretion and its biogenesis","volume":"48","year":"2021","journal-title":"Mol. Biol. Rep."},{"key":"2022103115571361000_BST-2022-0204CC85","doi-asserted-by":"publisher","first-page":"712","DOI":"10.1038\/s41467-018-03111-4","article-title":"C-terminal calcium binding of \u03b1-synuclein modulates synaptic vesicle interaction","volume":"9","year":"2018","journal-title":"Nat. Commun."},{"key":"2022103115571361000_BST-2022-0204CC86","doi-asserted-by":"publisher","first-page":"e15353","DOI":"10.1371\/journal.pone.0015353","article-title":"Exosomes communicate protective messages during oxidative stress; possible role of exosomal shuttle RNA","volume":"5","year":"2010","journal-title":"PLoS One"},{"key":"2022103115571361000_BST-2022-0204CC87","doi-asserted-by":"publisher","first-page":"929","DOI":"10.3390\/antiox9100929","article-title":"Microvesicle formation induced by oxidative stress in human erythrocytes","volume":"9","year":"2020","journal-title":"Antioxidants (Basel)"},{"key":"2022103115571361000_BST-2022-0204CC88","doi-asserted-by":"publisher","first-page":"52","DOI":"10.1016\/j.neurobiolaging.2017.09.016","article-title":"Intercellular transfer of pathogenic \u03b1-synuclein by extracellular vesicles is induced by the lipid peroxidation product 4-hydroxynonenal","volume":"61","year":"2018","journal-title":"Neurobiol. Aging"},{"key":"2022103115571361000_BST-2022-0204CC89","doi-asserted-by":"publisher","first-page":"1931","DOI":"10.1073\/pnas.1520335113","article-title":"\u03b1-Synuclein\u2013induced lysosomal dysfunction occurs through disruptions in protein trafficking in human midbrain synucleinopathy models","volume":"113","year":"2016","journal-title":"Proc. Natl Acad. Sci. U.S.A."},{"key":"2022103115571361000_BST-2022-0204CC90","doi-asserted-by":"publisher","first-page":"12535","DOI":"10.1523\/JNEUROSCI.1920-10.2010","article-title":"Pathogenic lysosomal depletion in Parkinson's disease","volume":"30","year":"2010","journal-title":"J. Neurosci."},{"key":"2022103115571361000_BST-2022-0204CC91","doi-asserted-by":"publisher","first-page":"98","DOI":"10.4161\/auto.7.1.13933","article-title":"Lysosomal membrane permeabilization in Parkinson disease","volume":"7","year":"2011","journal-title":"Autophagy"},{"key":"2022103115571361000_BST-2022-0204CC92","doi-asserted-by":"publisher","first-page":"98","DOI":"10.1080\/15548627.2017.1395992","article-title":"Autophagy inhibition promotes SNCA\/alpha-synuclein release and transfer via extracellular vesicles with a hybrid autophagosome-exosome-like phenotype","volume":"14","year":"2018","journal-title":"Autophagy"},{"key":"2022103115571361000_BST-2022-0204CC93","doi-asserted-by":"publisher","first-page":"1020","DOI":"10.1080\/15548627.2021.1967615","article-title":"LGALS3 (galectin 3) mediates an unconventional secretion of SNCA\/\u03b1-synuclein in response to lysosomal membrane damage by the autophagic-lysosomal pathway in human midbrain dopamine neurons","volume":"18","year":"2022","journal-title":"Autophagy"},{"key":"2022103115571361000_BST-2022-0204CC94","doi-asserted-by":"publisher","first-page":"1327","DOI":"10.3390\/biom10091327","article-title":"Extracellular vesicles as nanotherapeutics for Parkinson's disease","volume":"10","year":"2020","journal-title":"Biomolecules"},{"key":"2022103115571361000_BST-2022-0204CC95","doi-asserted-by":"publisher","first-page":"1438","DOI":"10.14336\/AD.2021.0516","article-title":"Extracellular vesicles for the diagnosis and treatment of Parkinson's disease","volume":"12","year":"2021","journal-title":"Aging Dis."},{"key":"2022103115571361000_BST-2022-0204CC96","doi-asserted-by":"publisher","first-page":"47","DOI":"10.1186\/s12964-021-00730-1","article-title":"The exosome journey: from biogenesis to uptake and intracellular signalling","volume":"19","year":"2021","journal-title":"Cell Commun. Signal."},{"key":"2022103115571361000_BST-2022-0204CC97","doi-asserted-by":"publisher","first-page":"4444","DOI":"10.1021\/acsnano.9b10033","article-title":"Endocytosis of extracellular vesicles and release of their cargo from endosomes","volume":"14","year":"2020","journal-title":"ACS Nano"},{"key":"2022103115571361000_BST-2022-0204CC98","doi-asserted-by":"publisher","first-page":"344","DOI":"10.3389\/fnins.2018.00344","article-title":"Import and export of misfolded \u03b1-synuclein","volume":"12","year":"2018","journal-title":"Front. Neurosci."},{"key":"2022103115571361000_BST-2022-0204CC99","doi-asserted-by":"publisher","first-page":"37530","DOI":"10.1074\/jbc.M305266200","article-title":"Structural organization of alpha-synuclein fibrils studied by site-directed spin labeling","volume":"278","year":"2003","journal-title":"J. Biol. Chem."},{"key":"2022103115571361000_BST-2022-0204CC100","doi-asserted-by":"publisher","first-page":"2397","DOI":"10.1016\/j.jmb.2013.01.040","article-title":"Nanobodies raised against monomeric \u03b1-synuclein distinguish between fibrils at different maturation stages","volume":"425","year":"2013","journal-title":"J. Mol. Biol."},{"key":"2022103115571361000_BST-2022-0204CC101","doi-asserted-by":"publisher","first-page":"57","DOI":"10.1186\/s12915-017-0390-6","article-title":"Nanobodies raised against monomeric \u0251-synuclein inhibit fibril formation and destabilize toxic oligomeric species","volume":"15","year":"2017","journal-title":"BMC Biol."},{"key":"2022103115571361000_BST-2022-0204CC102","doi-asserted-by":"publisher","first-page":"470","DOI":"10.3389\/fimmu.2013.00470","article-title":"Heparan sulfate: a ubiquitous glycosaminoglycan with multiple roles in immunity","volume":"4","year":"2013","journal-title":"Front. Immunol."},{"key":"2022103115571361000_BST-2022-0204CC103","doi-asserted-by":"publisher","first-page":"38","DOI":"10.1186\/1750-1326-7-38","article-title":"Suppression of dynamin GTPase decreases \u03b1-synuclein uptake by neuronal and oligodendroglial cells: a potent therapeutic target for synucleinopathy","volume":"7","year":"2012","journal-title":"Mol. Neurodegener."},{"key":"2022103115571361000_BST-2022-0204CC104","doi-asserted-by":"publisher","first-page":"452","DOI":"10.1111\/febs.15349","article-title":"Pharmacological inhibition and knockdown of O-GlcNAcase reduces cellular internalization of \u03b1-synuclein preformed fibrils","volume":"288","year":"2021","journal-title":"FEBS J."},{"key":"2022103115571361000_BST-2022-0204CC105","doi-asserted-by":"publisher","first-page":"382","DOI":"10.3389\/fnins.2019.00382","article-title":"Differential aggregation and phosphorylation of alpha synuclein in membrane compartments associated With Parkinson disease","volume":"13","year":"2019","journal-title":"Front. Neurosci."},{"key":"2022103115571361000_BST-2022-0204CC106","doi-asserted-by":"publisher","first-page":"20305","DOI":"10.1073\/pnas.1922741117","article-title":"Parkinson's disease-related phosphorylation at Tyr39 rearranges \u03b1-synuclein amyloid fibril structure revealed by cryo-EM","volume":"117","year":"2020","journal-title":"Proc. Natl Acad. Sci. U.S.A."},{"key":"2022103115571361000_BST-2022-0204CC107","doi-asserted-by":"publisher","first-page":"4374","DOI":"10.1074\/jbc.M115.705095","article-title":"Effects of serine 129 phosphorylation on \u03b1-synuclein aggregation, membrane association, and internalization","volume":"291","year":"2016","journal-title":"J. Biol. Chem."},{"key":"2022103115571361000_BST-2022-0204CC108","doi-asserted-by":"publisher","first-page":"1163","DOI":"10.1038\/s41598-022-04780-4","article-title":"Phosphorylation of endogenous \u03b1-synuclein induced by extracellular seeds initiates at the pre-synaptic region and spreads to the cell body","volume":"12","year":"2022","journal-title":"Sci. Rep."},{"key":"2022103115571361000_BST-2022-0204CC109","doi-asserted-by":"publisher","first-page":"20","DOI":"10.1186\/2047-9158-2-20","article-title":"Uptake and mitochondrial dysfunction of alpha-synuclein in human astrocytes, cortical neurons and fibroblasts","volume":"2","year":"2013","journal-title":"Transl. Neurodegener."},{"key":"2022103115571361000_BST-2022-0204CC110","doi-asserted-by":"publisher","first-page":"591475","DOI":"10.3389\/fnagi.2021.591475","article-title":"Exogenous alpha-synuclein evoked parkin downregulation promotes mitochondrial dysfunction in neuronal cells. implications for Parkinson's disease pathology","volume":"13","year":"2021","journal-title":"Front. Aging Neurosci."},{"key":"2022103115571361000_BST-2022-0204CC111","doi-asserted-by":"publisher","first-page":"7813","DOI":"10.1073\/pnas.1713129115","article-title":"\u03b1-Synuclein oligomers induce early axonal dysfunction in human iPSC-based models of synucleinopathies","volume":"115","year":"2018","journal-title":"Proc. Natl Acad. Sci. U.S.A."},{"key":"2022103115571361000_BST-2022-0204CC112","doi-asserted-by":"publisher","first-page":"3217","DOI":"10.1093\/brain\/aww238","article-title":"A de novo compound targeting \u03b1-synuclein improves deficits in models of Parkinson's disease","volume":"139","year":"2016","journal-title":"Brain"},{"key":"2022103115571361000_BST-2022-0204CC113","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1038\/s41419-018-0816-2","article-title":"Exosomal secretion of \u03b1-synuclein as protective mechanism after upstream blockage of macroautophagy","volume":"9","year":"2018","journal-title":"Cell Death Dis."},{"key":"2022103115571361000_BST-2022-0204CC114","doi-asserted-by":"publisher","first-page":"2506","DOI":"10.1021\/acschemneuro.0c00332","article-title":"Classics in chemical neuroscience: pramipexole","volume":"11","year":"2020","journal-title":"ACS Chem. Neurosci."},{"key":"2022103115571361000_BST-2022-0204CC115","doi-asserted-by":"publisher","first-page":"1373","DOI":"10.3892\/etm.2016.3471","article-title":"Effects of pramipexole treatment on the \u03b1-synuclein content in serum exosomes of Parkinson's disease patients","volume":"12","year":"2016","journal-title":"Exp. Ther. Med."},{"key":"2022103115571361000_BST-2022-0204CC116","doi-asserted-by":"publisher","first-page":"495","DOI":"10.1007\/s00401-021-02324-0","article-title":"\u03b1-Synuclein in blood exosomes immunoprecipitated using neuronal and oligodendroglial markers distinguishes Parkinson's disease from multiple system atrophy","volume":"142","year":"2021","journal-title":"Acta Neuropathol."}],"container-title":["Biochemical Society Transactions"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/portlandpress.com\/biochemsoctrans\/article-pdf\/50\/5\/1303\/938970\/bst-2022-0204c.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/portlandpress.com\/biochemsoctrans\/article-pdf\/50\/5\/1303\/938970\/bst-2022-0204c.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,10,31]],"date-time":"2022-10-31T15:57:25Z","timestamp":1667231845000},"score":1,"resource":{"primary":{"URL":"https:\/\/portlandpress.com\/biochemsoctrans\/article\/50\/5\/1303\/231816\/Propagation-of-Parkinson-s-disease-by"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,9,16]]},"references-count":116,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2022,9,16]]},"published-print":{"date-parts":[[2022,10,31]]}},"URL":"https:\/\/doi.org\/10.1042\/bst20220204","relation":{},"ISSN":["0300-5127","1470-8752"],"issn-type":[{"value":"0300-5127","type":"print"},{"value":"1470-8752","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,9,16]]}}}