Galectin-3 shapes toxic alpha-synuclein strains in Parkinson’s disease
© The Author(s) 2023. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, p...
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| Formato: | artículo |
| Estado: | Versión publicada |
| Fecha de publicación: | 2023 |
| País: | España |
| Recursos: | Consejo Superior de Investigaciones Científicas (CSIC) |
| Repositorio: | DIGITAL.CSIC. Repositorio Institucional del CSIC |
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| Palavra-chave: | Parkinson’s disease (PD) Galectin-3 (GAL3) α-synuclein (αSYN) Lewy body (LB) |
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Galectin-3 shapes toxic alpha-synuclein strains in Parkinson’s disease |
| title |
Galectin-3 shapes toxic alpha-synuclein strains in Parkinson’s disease |
| spellingShingle |
Galectin-3 shapes toxic alpha-synuclein strains in Parkinson’s disease García-Revilla, Juan Parkinson’s disease (PD) Galectin-3 (GAL3) α-synuclein (αSYN) Lewy body (LB) |
| title_short |
Galectin-3 shapes toxic alpha-synuclein strains in Parkinson’s disease |
| title_full |
Galectin-3 shapes toxic alpha-synuclein strains in Parkinson’s disease |
| title_fullStr |
Galectin-3 shapes toxic alpha-synuclein strains in Parkinson’s disease |
| title_full_unstemmed |
Galectin-3 shapes toxic alpha-synuclein strains in Parkinson’s disease |
| title_sort |
Galectin-3 shapes toxic alpha-synuclein strains in Parkinson’s disease |
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García-Revilla, Juan Boza-Serrano, Antonio Jin, Yiyun Vadukul, Devkee M. Soldán-Hidalgo, Jesús Camprubí-Ferrer, Lluís García-Cruzado, Marta Martinsson, Isak Klementieva, Oxana Ruiz, Rocío Aprile, Francesco A. Deierborg, Tomas Venero, José L. |
| author |
García-Revilla, Juan |
| author_facet |
García-Revilla, Juan Boza-Serrano, Antonio Jin, Yiyun Vadukul, Devkee M. Soldán-Hidalgo, Jesús Camprubí-Ferrer, Lluís García-Cruzado, Marta Martinsson, Isak Klementieva, Oxana Ruiz, Rocío Aprile, Francesco A. Deierborg, Tomas Venero, José L. |
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author |
| author2 |
Boza-Serrano, Antonio Jin, Yiyun Vadukul, Devkee M. Soldán-Hidalgo, Jesús Camprubí-Ferrer, Lluís García-Cruzado, Marta Martinsson, Isak Klementieva, Oxana Ruiz, Rocío Aprile, Francesco A. Deierborg, Tomas Venero, José L. |
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author author author author author author author author author author author author |
| dc.contributor.none.fl_str_mv |
Michael J. Fox Foundation for Parkinson's Research Lund University Hospital Clínic de Barcelona Institut d'Investigacions Biomèdiques August Pi i Sunyer Universidad de Barcelona Ministerio de Universidades (España) European Commission Dementia Association (Sweden) Swedish Brain Foundation Crafoord Foundation Olle Engkvist Foundation Gamla Tjänarinnor Foundation Swedish Medical Research Council Swedish Parkinson Foundation Fredrik O Ingrid Thurings Foundation Swedish National Association for Social and Mental Health Swedish Research Council Ministerio de Ciencia e Innovación (España) Agencia Estatal de Investigación (España) Junta de Andalucía UK Research and Innovation Alzheimer's Research UK Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72] |
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Parkinson’s disease (PD) Galectin-3 (GAL3) α-synuclein (αSYN) Lewy body (LB) |
| topic |
Parkinson’s disease (PD) Galectin-3 (GAL3) α-synuclein (αSYN) Lewy body (LB) |
| description |
© The Author(s) 2023. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. |
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2023 |
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2023 2024 2024 |
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info:eu-repo/semantics/article http://purl.org/coar/resource_type/c_6501 Publisher's version info:eu-repo/semantics/publishedVersion |
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Galectin-3 shapes toxic alpha-synuclein strains in Parkinson’s diseaseGarcía-Revilla, JuanBoza-Serrano, AntonioJin, YiyunVadukul, Devkee M.Soldán-Hidalgo, JesúsCamprubí-Ferrer, LluísGarcía-Cruzado, MartaMartinsson, IsakKlementieva, OxanaRuiz, RocíoAprile, Francesco A.Deierborg, TomasVenero, José L.Parkinson’s disease (PD)Galectin-3 (GAL3)α-synuclein (αSYN)Lewy body (LB)© The Author(s) 2023. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.Parkinson’s Disease (PD) is a neurodegenerative and progressive disorder characterised by intracytoplasmic inclusions called Lewy bodies (LB) and degeneration of dopaminergic neurons in the substantia nigra (SN). Aggregated α-synuclein (αSYN) is known to be the main component of the LB. It has also been reported to interact with several proteins and organelles. Galectin-3 (GAL3) is known to have a detrimental function in neurodegenerative diseases. It is a galactose-binding protein without known catalytic activity and is expressed mainly by activated microglial cells in the central nervous system (CNS). GAL3 has been previously found in the outer layer of the LB in post-mortem brains. However, the role of GAL3 in PD is yet to be elucidated. In post-mortem samples, we identified an association between GAL3 and LB in all the PD subjects studied. GAL3 was linked to less αSYN in the LB outer layer and other αSYN deposits, including pale bodies. GAL3 was also associated with disrupted lysosomes. In vitro studies demonstrate that exogenous recombinant Gal3 is internalised by neuronal cell lines and primary neurons where it interacts with endogenous αSyn fibrils. In addition, aggregation experiments show that Gal3 affects spatial propagation and the stability of pre-formed αSyn fibrils resulting in short, amorphous toxic strains. To further investigate these observations in vivo, we take advantage of WT and Gal3KO mice subjected to intranigral injection of adenovirus overexpressing human αSyn as a PD model. In line with our in vitro studies, under these conditions, genetic deletion of GAL3 leads to increased intracellular αSyn accumulation within dopaminergic neurons and remarkably preserved dopaminergic integrity and motor function. Overall, our data suggest a prominent role for GAL3 in the aggregation process of αSYN and LB formation, leading to the production of short species to the detriment of larger strains which triggers neuronal degeneration in a mouse model of PD.This work was supported by The Michael J. Fox Foundation For Parkinson's Research (Grant ID: 11902). DLB samples were kindly provided by Elisabet Englund (Lund University) and PD samples were obtained with the help of Raquel Sánchez-Valle (Hospital Clínic de Barcelona, IDIBAPS, Universitat de Barcelona). J.G-R is granted by Spanish Ministerio de Universidades/NexGenerationEU/Ayudas Margarita Salas (20117) and Swedish Demensfonden. The Strategic Research Area MultiPark (Multidisciplinary Research in neurodegenerative diseases) at Lund University, the Swedish Brain Foundation, Crafoord Foundation, Swedish Dementia Association, G&J Kock Foundation, Olle Engkvist Foundation, Gamla Tjänarinnor Foundation, the Swedish Medical Research Council, the Swedish Parkinson Foundation, the Swedish Parkinson Research Foundation the A.E. Berger Foundation, the Thurings Foundation, and the Swedish mental health foundation to T.D., I.M., and The Swedish Research Council (International postdoc, 2019-06333) to A.B-S. We also thank the Spanish Ministerio de Ciencia e Innovación/FEDER/UE/PID2021-124096OB-I00; the Spanish Junta de Andalucia/FEDER/EU P18-RT-1372, the Spanish FEDER I + D + i-USE US-1264806, and the Agencia Española de Investigación PID2021-124096OB-I00 to J.L.V, and R.R. We thank the Agencia Española de Investigación PID2021-124096OB-I00 and the Spanish Junta de Andalucia /FEDER/EU P18-RT-1372. FAA is grateful to UK Research and Innovation (Future Leaders Fellowship MR/S033947/1), Alzheimer’s Society, UK (Grant 511), and Alzheimer’s Research UK (ARUK-PG2019B-020) for the support.Open access funding provided by Lund University.Peer reviewedSpringer NatureMichael J. Fox Foundation for Parkinson's ResearchLund UniversityHospital Clínic de BarcelonaInstitut d'Investigacions Biomèdiques August Pi i SunyerUniversidad de BarcelonaMinisterio de Universidades (España)European CommissionDementia Association (Sweden)Swedish Brain FoundationCrafoord FoundationOlle Engkvist FoundationGamla Tjänarinnor FoundationSwedish Medical Research CouncilSwedish Parkinson FoundationFredrik O Ingrid Thurings FoundationSwedish National Association for Social and Mental HealthSwedish Research CouncilMinisterio de Ciencia e Innovación (España)Agencia Estatal de Investigación (España)Junta de AndalucíaUK Research and InnovationAlzheimer's Research UKConsejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]202420242023info:eu-repo/semantics/articlehttp://purl.org/coar/resource_type/c_6501Publisher's versioninfo:eu-repo/semantics/publishedVersionapplication/pdfhttp://hdl.handle.net/10261/350461reponame:DIGITAL.CSIC. Repositorio Institucional del CSICinstname:Consejo Superior de Investigaciones Científicas (CSIC)Inglés#PLACEHOLDER_PARENT_METADATA_VALUE##PLACEHOLDER_PARENT_METADATA_VALUE##PLACEHOLDER_PARENT_METADATA_VALUE#info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2021-2023/PID2021-124096OB-I00info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2021-2023/PID2021-124096OB-I00info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2021-2023/PID2021-124096OB-I00The underlying dataset has been published as supplementary material of the article in the publisher platform at https://doi.org/10.1007/s00401-023-02585-xhttps://doi.org/10.1007/s00401-023-02585-xSíinfo:eu-repo/semantics/openAccessoai:digital.csic.es:10261/3504612026-05-22T06:33:51Z |
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