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Artículo
The role of Galectin-3 in α-synuclein-induced microglial activation
Autor/es | Boza Serrano, Antonio
Reyes, Juan F. Rey, Nolwen L. Leffler, Hakon Bousset, Luc Nilsson, Ulf J. Brundin, Patrik Venero Recio, José Luis Burguillos García, Miguel Ángel Deierborg, Tomas |
Departamento | Universidad de Sevilla. Departamento de Bioquímica y Biología Molecular |
Fecha de publicación | 2014 |
Fecha de depósito | 2016-05-24 |
Publicado en |
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Resumen | 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 ... 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 |
Cita | 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. |
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