dc.creator | García Revilla, Juan | es |
dc.creator | Boza Serrano, Antonio | es |
dc.creator | Jin, Yiyun | es |
dc.creator | Vadukul, Devkee M. | es |
dc.creator | Soldán Hidalgo, Jesús | es |
dc.creator | Camprubí Ferrer, Lluís | es |
dc.creator | Ruiz Laza, Rocío | es |
dc.creator | Venero Recio, José Luis | es |
dc.date.accessioned | 2023-06-20T10:03:49Z | |
dc.date.available | 2023-06-20T10:03:49Z | |
dc.date.issued | 2023 | |
dc.identifier.citation | García Revilla, J., Boza Serrano, A., Jin, Y., Vadukul, D.M., Soldán Hidalgo, J., Camprubí Ferrer, L.,...,Venero Recio, J.L. (2023). Galectin-3 shapes toxic alpha-synuclein strains in Parkinson's disease.. Acta Neuropathologica, 146, 51-75. https://doi.org/10.1007/s00401-023-02585-x. | |
dc.identifier.issn | 0001-6322 | es |
dc.identifier.issn | 1432-0533 | es |
dc.identifier.uri | https://hdl.handle.net/11441/147349 | |
dc.description.abstract | 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 identifed 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 fbrils. In addition, aggregation experiments show that Gal3 afects spatial propagation and the stability of pre-formed αSyn fbrils 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. | es |
dc.description.sponsorship | The Michael J. Fox Foundation for Parkinson's Research ID: 11902 | es |
dc.description.sponsorship | Ministerio de Ciencia e Innovación de España/FEDER/UE/PID2021-124096OB-I00 | es |
dc.description.sponsorship | Junta de Andalucía/FEDER/EU P18-RT-1372 | es |
dc.description.sponsorship | FEDER I + D + i-USE US-1264806 | es |
dc.description.sponsorship | UK Research and Innovation - Future Leaders Fellowship MR/S033947/1 | es |
dc.description.sponsorship | Alzheimer’s Society, UK - Grant 51 | es |
dc.description.sponsorship | Alzheimer’s Research. UK - ARUK-PG2019B-020 | es |
dc.format | application/pdf | es |
dc.format.extent | 25 p. | es |
dc.language.iso | eng | es |
dc.publisher | Springer | es |
dc.relation.ispartof | Acta Neuropathologica, 146, 51-75. | |
dc.rights | Atribución 4.0 Internacional | * |
dc.rights.uri | http://creativecommons.org/licenses/by/4.0/ | * |
dc.subject | Parkinson’s disease (PD) | es |
dc.subject | Galectin-3 (GAL3) | es |
dc.subject | α-synuclein (αSYN) | es |
dc.subject | Lewy body (LB) | es |
dc.title | Galectin-3 shapes toxic alpha-synuclein strains in Parkinson's disease. | es |
dc.type | info:eu-repo/semantics/article | es |
dcterms.identifier | https://ror.org/03yxnpp24 | |
dc.type.version | info:eu-repo/semantics/publishedVersion | es |
dc.rights.accessRights | info:eu-repo/semantics/openAccess | es |
dc.contributor.affiliation | Universidad de Sevilla. Departamento de Bioquímica y Biología Molecular | es |
dc.relation.projectID | PID2021-124096OB-I00 | es |
dc.relation.projectID | P18-RT-1372 | es |
dc.relation.projectID | FEDER I + D + i-USE US-1264806 | es |
dc.relation.projectID | MR/S033947/1 | es |
dc.relation.projectID | ARUK-PG2019B-020 | es |
dc.relation.publisherversion | https://doi.org/10.1007/s00401-023-02585-x | es |
dc.identifier.doi | 10.1007/s00401-023-02585-x | es |
dc.journaltitle | Acta Neuropathologica | es |
dc.publication.volumen | 146 | es |
dc.publication.initialPage | 51 | es |
dc.publication.endPage | 75 | es |
dc.contributor.funder | The Michael J. Fox Foundation for Parkinson's Research | es |
dc.contributor.funder | Ministerio de Ciencia e Innovación (MICIN). España | es |
dc.contributor.funder | European Commission (EC). Fondo Europeo de Desarrollo Regional (FEDER) | es |
dc.contributor.funder | Junta de Andalucía | es |
dc.contributor.funder | Universidad de Sevilla | es |
dc.contributor.funder | Agencia Estatal de Investigación. España | es |
dc.contributor.funder | UK Research and Innovation | es |
dc.contributor.funder | Alzheimer’s Society, UK | es |
dc.contributor.funder | Alzheimer’s Research. UK | es |
dc.description.awardwinning | Premio Anual Publicación Científica Destacada de la US. Facultad de Farmacia | |