Sökning: WFRF:(Venero José Luis)
> (2014) >
The role of Galecti...
The role of Galectin-3 in α-synuclein-induced microglial activation
-
- Boza-Serrano, Antonio (författare)
- Lund University,Lunds universitet,Neuroinflammation,Forskargrupper vid Lunds universitet,Lund University Research Groups
-
- Reyes, Juan F. (författare)
- Lund University,Lunds universitet,Institutionen för experimentell medicinsk vetenskap,Medicinska fakulteten,Department of Experimental Medical Science,Faculty of Medicine
-
- Rey, Nolwen L. (författare)
- Lund University,Lunds universitet,Institutionen för experimentell medicinsk vetenskap,Medicinska fakulteten,Department of Experimental Medical Science,Faculty of Medicine,Van Andel Research Institute
-
visa fler...
-
- Leffler, Hakon (författare)
- Lund University,Lunds universitet,Avdelningen för mikrobiologi, immunologi och glykobiologi - MIG,Institutionen för laboratoriemedicin,Medicinska fakulteten,Division of Microbiology, Immunology and Glycobiology - MIG,Department of Laboratory Medicine,Faculty of Medicine
-
- Bousset, Luc (författare)
- LEBS Laboratoire d'Enzymologie et Biochimie Structurales CNRS
-
- Nilsson, Ulf (författare)
- Lund University,Lunds universitet,Centrum för analys och syntes,Kemiska institutionen,Institutioner vid LTH,Lunds Tekniska Högskola,Centre for Analysis and Synthesis,Department of Chemistry,Departments at LTH,Faculty of Engineering, LTH
-
- Brundin, Patrik (författare)
- Lund University,Lunds universitet,Institutionen för experimentell medicinsk vetenskap,Medicinska fakulteten,Department of Experimental Medical Science,Faculty of Medicine,Van Andel Research Institute
-
- Venero, Jose Luis (författare)
- University of Seville
-
- Burguillos, Miguel Angel (författare)
- Karolinska Institute
-
- Deierborg, Tomas (författare)
- Lund University,Lunds universitet,Neuroinflammation,Forskargrupper vid Lunds universitet,Lund University Research Groups
-
visa färre...
-
(creator_code:org_t)
- 2014-11-12
- 2014
- Engelska.
-
Ingår i: Acta Neuropathologica Communications. - : Springer Science and Business Media LLC. - 2051-5960. ; 2
- Relaterad länk:
-
http://dx.doi.org/10... (free)
-
visa fler...
-
https://actaneurocom...
-
https://lup.lub.lu.s...
-
https://doi.org/10.1...
-
http://kipublication...
-
visa färre...
Abstract
Ämnesord
Stäng
- 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-1β) 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-1H-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.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Neurologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Neurology (hsv//eng)
Nyckelord
- Galectin-3
- Microglia
- Neuroinflammation
- Parkinson's disease
- α-synuclein
Publikations- och innehållstyp
- for (ämneskategori)
- ref (ämneskategori)
Hitta via bibliotek
Till lärosätets databas
- Av författaren/redakt...
-
Boza-Serrano, An ...
-
Reyes, Juan F.
-
Rey, Nolwen L.
-
Leffler, Hakon
-
Bousset, Luc
-
Nilsson, Ulf
-
visa fler...
-
Brundin, Patrik
-
Venero, Jose Lui ...
-
Burguillos, Migu ...
-
Deierborg, Tomas
-
visa färre...
- Om ämnet
-
- MEDICIN OCH HÄLSOVETENSKAP
-
MEDICIN OCH HÄLS ...
-
och Klinisk medicin
-
och Neurologi
- Artiklar i publikationen
-
Acta Neuropathol ...
- Av lärosätet
-
Lunds universitet
-
Karolinska Institutet