dc.creator | Boza Serrano, Antonio | es |
dc.creator | Reyes, Juan F. | es |
dc.creator | Rey, Nolwen L. | es |
dc.creator | Leffler, Hakon | es |
dc.creator | Bousset, Luc | es |
dc.creator | Nilsson, Ulf J. | es |
dc.creator | Brundin, Patrik | es |
dc.creator | Venero Recio, José Luis | es |
dc.creator | Burguillos García, Miguel Ángel | es |
dc.creator | Deierborg, Tomas | es |
dc.date.accessioned | 2016-05-24T12:34:42Z | |
dc.date.available | 2016-05-24T12:34:42Z | |
dc.date.issued | 2014 | |
dc.identifier.citation | Boza Serrano, A., Reyes, J.F., Rey, N.L., Leffler, H., Bousset, L., Nilsson, U.J.,...,Deierborg, T. (2014). The role of Galectin-3 in α-synuclein-induced microglial activation. Acta neuropathologica communications, 2, 1-14. | |
dc.identifier.issn | 2051-5960 | es |
dc.identifier.uri | http://hdl.handle.net/11441/41539 | |
dc.description.abstract | Background:
Parkinson
’
s disease (PD) is the most prevalent neurodegenerative motor disorder. The neuropathology is
characterized by intraneuronal protein aggregates of
α
-synuclein and progressive degeneration of dopaminergic
neurons within the substantia nigra. Previous studies have shown that extracellular
α
-synuclein aggregates can activate
microglial cells, induce inflammation and contribute to the neurodegenerative process in PD. However, the signaling
pathways involved in
α
-synuclein-mediated microglia activation are poorly understood. Galectin-3 is a member of a
carbohydrate-binding protein family involved in cell activation and inflammation. Therefore, we investigated whether
galectin-3 is involved in the microglia activation triggered by
α
-synuclein.
Results:
We cultured microglial (BV2) cells and induced cell activation by addition of exogenous
α
-synuclein monomers
or aggregates to the cell culture medium. This treatment induced a significant increase in the levels of proinflammatory
mediators including the inducible Nitric Oxide Synthase (iNOS), interleukin 1 Beta (IL-1
β
) and Interleukin-12 (IL-12). We
then reduced the levels of galectin-3 expression using siRNA or pharmacologically targeting galectin-3 activity using
bis-(3-deoxy-3-(3-fluorophenyl-1
H
-1,2,3-triazol-1-yl)-
β
-D-galactopyranosyl)-sulfane. Both approaches led to a significant
reduction in the observed inflammatory response induced by
α
-synuclein. We confirmed these findings using primary
microglial cells obtained from wild-type and galectin-3 null mutant mice. Finally, we performed injections of
α
-synuclein in the olfactory bulb of wild type mice and observed that some of the
α
-synuclein was taken up by
activated microglia that were immunopositive for galectin-3.
Conclusions:
We show that
α
-synuclein aggregates induce microglial activation and demonstrate for the first time that
galectin-3 plays a significant role in microglia activation induced by
α
-synuclein. These results suggest that genetic
down-regulation or pharmacological inhibition of galectin-3 might constitute a novel therapeutic target in PD and
other synucleinopathies | es |
dc.format | application/pdf | es |
dc.language.iso | eng | es |
dc.publisher | BioMed Central | es |
dc.relation.ispartof | Acta neuropathologica communications, 2, 1-14. | |
dc.rights | Attribution-NonCommercial-NoDerivatives 4.0 Internacional | * |
dc.rights.uri | http://creativecommons.org/licenses/by-nc-nd/4.0/ | * |
dc.subject | Microglia | es |
dc.subject | Galectin-3 | es |
dc.subject | Neuroinflammation | es |
dc.subject | α -synuclein | es |
dc.subject | Parkinson’s disease | es |
dc.title | The role of Galectin-3 in α-synuclein-induced microglial activation | 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.publisherversion | 10.1186/s40478-014-0156-0 | es |
dc.identifier.doi | http://dx.doi.org/10.1186/s40478-014-0156-0 | es |
dc.contributor.group | Universidad de Sevilla. BIO113: Mecanismos de Muerte Celular en Enfermedades Neurodegenerativas | es |
idus.format.extent | 14 p. | es |
dc.journaltitle | Acta neuropathologica communications | es |
dc.publication.volumen | 2 | es |
dc.publication.initialPage | 1 | es |
dc.publication.endPage | 14 | es |
dc.identifier.idus | https://idus.us.es/xmlui/handle/11441/41539 | |