Publication:
LRRK2 interactions with α-synuclein in Parkinson’s disease brains and in cell models
LRRK2 interactions with α-synuclein in Parkinson’s disease brains and in cell models
dc.contributor.author | Guirreiro, Patricia Silva | en_US |
dc.contributor.author | Huang, Yue | en_US |
dc.contributor.author | Gysbers, Amanda | en_US |
dc.contributor.author | Cheng, Danni | en_US |
dc.contributor.author | Gai, Wei Ping | en_US |
dc.contributor.author | Outeiro, Tiago Fleming | en_US |
dc.contributor.author | Halliday, Glenda | en_US |
dc.date.accessioned | 2021-11-25T12:29:13Z | |
dc.date.available | 2021-11-25T12:29:13Z | |
dc.date.issued | 2013 | en_US |
dc.description.abstract | Mutations in the genes encoding leucine-rich repeat kinase 2 (LRRK2) and α-synuclein are associated with both autosomal dominant and idiopathic forms of Parkinson’s disease (PD). α-Synuclein is the main protein in Lewy bodies, hallmark inclusions present in both sporadic and familial PD. We show that in PD brain tissue, the levels of LRRK2 are positively related to the increase in α-synuclein phosphorylation and aggregation in affected brain regions (amygdala and anterior cingulate cortex), but not in the unaffected visual cortex. In disease-affected regions, we show co-localization of these two proteins in neurons and Lewy body inclusions. Further in vitro experiments show a molecular interaction between α-synuclein and LRRK2 under endogenous and over-expression conditions. In a cell culture model of α-synuclein inclusion formation, LRRK2 co-localizes with the α-synuclein inclusions, and knocking down LRRK2 increases the number of smaller inclusions. In addition to providing strong evidence for an interaction between LRRK2 and α-synuclein, our results shed light on the complex relationship between these two proteins in the brains of patients with PD and the underlying molecular mechanisms of the disease. | en_US |
dc.identifier.issn | 0946-2716 | en_US |
dc.identifier.uri | http://hdl.handle.net/1959.4/53601 | |
dc.language | English | |
dc.language.iso | EN | en_US |
dc.rights | CC BY-NC-ND 3.0 | en_US |
dc.rights.uri | https://creativecommons.org/licenses/by-nc-nd/3.0/au/ | en_US |
dc.source | Legacy MARC | en_US |
dc.subject.other | Parkinson’s disease | en_US |
dc.subject.other | LRKK2 | en_US |
dc.subject.other | α-synuclein | en_US |
dc.subject.other | Lewy bodies | en_US |
dc.subject.other | interaction | en_US |
dc.title | LRRK2 interactions with α-synuclein in Parkinson’s disease brains and in cell models | en_US |
dc.type | Journal Article | en |
dcterms.accessRights | open access | |
dspace.entity.type | Publication | en_US |
unsw.accessRights.uri | https://purl.org/coar/access_right/c_abf2 | |
unsw.description.publisherStatement | The final publication is available at Springer via http://dx.doi.org/10.1007/s00109-012-0984-y | en_US |
unsw.identifier.doiPublisher | http://dx.doi.org/10.1007/s00109-012-0984-y | en_US |
unsw.relation.faculty | Medicine & Health | |
unsw.relation.ispartofissue | 4 | en_US |
unsw.relation.ispartofjournal | Journal of Molecular Medicine | en_US |
unsw.relation.ispartofpagefrompageto | 513-522 | en_US |
unsw.relation.ispartofvolume | 91 | en_US |
unsw.relation.originalPublicationAffiliation | Guirreiro, Patricia Silva, Cell and Molecular Neuroscience Unit, Instituto de Medicina Molecular, Lisboa, 04250 Portugal, Instituto de Fisiologia, Faculdade de Medicina da Universidade de Lisboa, Av. Professor Egas Moniz, 1649-028 Lisboa, 04250 Portugal | en_US |
unsw.relation.originalPublicationAffiliation | Huang, Yue, NeuRA | en_US |
unsw.relation.originalPublicationAffiliation | Gysbers, Amanda, NeuRA | en_US |
unsw.relation.originalPublicationAffiliation | Cheng, Danni, NeuRA | en_US |
unsw.relation.originalPublicationAffiliation | Gai, Wei Ping, Department of Human Physiology, The Centre for Neuroscience, Flinders University School of South Australia, 5042, Australia | en_US |
unsw.relation.originalPublicationAffiliation | Outeiro, Tiago Fleming, Cell and Molecular Neuroscience Unit, Instituto de Medicina Molecular, Lisboa, 04250 Portugal, dInstituto de Fisiologia, Faculdade de Medicina da Universidade de Lisboa, Av. Professor Egas Moniz, 1649-028 Lisboa, 04250 Portugal; eDepartment of Neurodegeneration and Restorative Research, University Medizin Goettingen, Waldweg 33, Goettingen, 37073 Germany | en_US |
unsw.relation.originalPublicationAffiliation | Halliday, Glenda, Neuroscience Research Australia, Faculty of Medicine, UNSW | en_US |
unsw.relation.school | Neuroscience Research Australia | * |
unsw.subject.fieldofresearchcode | 110903 Central Nervous System | en_US |
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