A light-inducible protein clustering system for in vivo analysis of α-synuclein aggregation in Parkinson disease

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dc.contributor.authorBérard, Morgan
dc.contributor.authorSheta, Razan
dc.contributor.authorMalvaut, Sarah
dc.contributor.authorRodriguez-Aller, Raquel
dc.contributor.authorTeixeira, Maxime
dc.contributor.authorIdi, Walid
dc.contributor.authorTurmel, Roxanne
dc.contributor.authorAlpaugh, Melanie
dc.contributor.authorDubois, Marilyn
dc.contributor.authorDahmene, Manel
dc.contributor.authorSalesse, Charleen
dc.contributor.authorLamontage-Proulx, Jérôme
dc.contributor.authorSt-Pierre, Marie-Kim
dc.contributor.authorTavassoly, Omid
dc.contributor.authorLuo, Wen
dc.contributor.authorDel Cid-Pellitero, Esther
dc.contributor.authorQazi, Raza
dc.contributor.authorJeong, Jae-Woong
dc.contributor.authorDurcan, Thomas M.
dc.contributor.authorVallières, Luc
dc.contributor.authorTremblay, Marie-Ève
dc.contributor.authorSoulet, Denis
dc.contributor.authorLévesque, Martin
dc.contributor.authorCicchetti, Francesca
dc.contributor.authorFon, Edward A.
dc.contributor.authorSaghatelyan, Armen
dc.contributor.authorOueslati, Abid
dc.date.accessioned2024-02-09T16:17:52Z
dc.date.available2024-02-09T16:17:52Z
dc.date.copyright2022en_US
dc.date.issued2022
dc.descriptionWe would like to thank Ms. Frédérique Larroquette from McGill University for her technical assistance.en_US
dc.description.abstractNeurodegenerative disorders refer to a group of diseases commonly associated with abnormal protein accumulation and aggregation in the central nervous system. However, the exact role of protein aggregation in the pathophysiology of these disorders remains unclear. This gap in knowledge is due to the lack of experimental models that allow for the spatiotemporal control of protein aggregation, and the investigation of early dynamic events associated with inclusion formation. Here, we report on the development of a light-inducible protein aggregation (LIPA) system that enables spatiotemporal control of α-synuclein (α-syn) aggregation into insoluble deposits called Lewy bodies (LBs), the pathological hallmark of Parkinson disease (PD) and other proteinopathies. We demonstrate that LIPA-α-syn inclusions mimic key biochemical, biophysical, and ultrastructural features of authentic LBs observed in PD-diseased brains. In vivo, LIPA-α-syn aggregates compromise nigrostriatal transmission, induce neurodegeneration and PD-like motor impairments. Collectively, our findings provide a new tool for the generation, visualization, and dissection of the role of α-syn aggregation in PD.en_US
dc.description.reviewstatusRevieweden_US
dc.description.scholarlevelFacultyen_US
dc.description.sponsorshipThis work was supported by Parkinson Society Canada, Fondation du CHU de Québec and the Canadian Institutes of Health Research (CIHR) grants to AO. AO was supported by Junior1 and Junior 2 salary Awards from the Fonds de Recherche du Québec - Santé (FRQS) and la Société Parkinson du Québec. In vivo Ca2+ imaging experiments were supported by the Canadian Institutes of Health Research (CIHR) grant to AS. MB was supported by scholarships from the Fondation du CHU de Québec, Faculty of Medicine of Université Laval (Bourse de recrutement du doctorat Pierre J. Durant), and FRQS. FC is a recipient of a Researcher Chair from the Fonds de Recherche du Québec en Santé (FRQS) and received funding from the Canadian Institutes of Health Research (CIHR). MA is supported by post-doctoral fellowships from both CIHR and FRQS. E.A.F. is supported by a Foundation grant from CIHR (FDN-154301) and a Canada Research Chair (Tier 1) in Parkinson’s disease. MKSP was supported by a Frederick Banting and Charles Best Canada Graduate Scholarship-Doctoral Award and a Doctoral's training scholarship from FRQS. MET is a Tier 2 Canada Research Chair in Neurobiology of Aging and Cognition. TMD is supported with funds from the McGill Healthy Brains for Healthy lives and a project grant from CIHR (PJT–169095). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.en_US
dc.identifier.citationBérard, M., Sheta, R., Malvaut, S., Rodriguez-Aller, R., Teixeira, M., Idi, W., ... Oueslati, A. (2022). A light-inducible protein clustering system for in vivo analysis of α-synuclein aggregation in Parkinson disease. PLoS Biology, 20(3), e3001578. https://doi.org/10.1371/journal.pbio.3001578en_US
dc.identifier.urihttps://doi.org/10.1371/journal.pbio.3001578
dc.identifier.urihttp://hdl.handle.net/1828/15979
dc.language.isoenen_US
dc.publisherPLoS Biologyen_US
dc.subjectneuronsen_US
dc.subjectdopaminergicsen_US
dc.subjectprotein aggregationen_US
dc.subjectmidbrainen_US
dc.subjectoptogeneticsen_US
dc.subjecttransfectionen_US
dc.subjectneostriatumen_US
dc.subjectconfocal microscopyen_US
dc.titleA light-inducible protein clustering system for in vivo analysis of α-synuclein aggregation in Parkinson diseaseen_US
dc.typeArticleen_US

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