Roodveldt, C;
Labrador-Garrido, A;
Gonzalez-Rey, E;
Fernandez-Montesinos, R;
Caro, M;
Lachaud, CC;
Waudby, CA;
... Pozo, D; + view all
(2010)
Glial Innate Immunity Generated by Non-Aggregated Alpha-Synuclein in Mouse: Differences between Wild-type and Parkinson's Disease-Linked Mutants.
PLOS ONE
, 5
(10)
, Article e13481. 10.1371/journal.pone.0013481.
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Abstract
Background: Parkinson's disease (PD) is a progressive neurodegenerative disorder characterized pathologically by the presence in the brain of intracellular protein inclusions highly enriched in aggregated alpha-synuclein (alpha-Syn). Although it has been established that progression of the disease is accompanied by sustained activation of microglia, the underlying molecules and factors involved in these immune-triggered mechanisms remain largely unexplored. Lately, accumulating evidence has shown the presence of extracellular alpha-Syn both in its aggregated and monomeric forms in cerebrospinal fluid and blood plasma. However, the effect of extracellular alpha-Syn on cellular activation and immune mediators, as well as the impact of familial PD-linked alpha-Syn mutants on this stimulation, are still largely unknown.Methods and Findings: In this work, we have compared the activation profiles of non-aggregated, extracellular wild-type and PD-linked mutant alpha-Syn variants on primary glial and microglial cell cultures. After stimulation of cells with alpha-Syn, we measured the release of Th1- and Th2-type cytokines as well as IP-10/CXCL10, RANTES/CCL5, MCP-1/CCL2 and MIP-1 alpha/CCL3 chemokines. Contrary to what had been observed using cell lines or for the case of aggregated alpha-Syn, we found strong differences in the immune response generated by wild-type alpha-Syn and the familial PD mutants (A30P, E46K and A53T).Conclusions: These findings might contribute to explain the differences in the onset and progression of this highly debilitating disease, which could be of value in the development of rational approaches towards effective control of immune responses that are associated with PD.
| Type: | Article |
|---|---|
| Title: | Glial Innate Immunity Generated by Non-Aggregated Alpha-Synuclein in Mouse: Differences between Wild-type and Parkinson's Disease-Linked Mutants |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1371/journal.pone.0013481 |
| Publisher version: | http://dx.doi.org/10.1371/journal.pone.0013481 |
| Language: | English |
| Additional information: | © 2010 Roodveldt et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. CR held a Federation of the Societies of Biochemistry and Molecular Biology Long-Term Fellowship during part of this work, and currently holds a postdoctoral fellowship by the Spanish Ministry of Science and Innovation (Juan de la Cierva Programme). RFM holds an FPI fellowship at the University of Seville Department of Normal and Pathological Cytology and Histology. This work was supported by Instituto de Salud Carlos III - Fund for Health of Spain (to MD and DP); Junta de Andalucia BIO-323 (DP) and CTS-541 (MD); Alicia Kloplowitz Foundation (to MD and DP); and Wellcome Trust and Leverhulme Trust grants (CMD). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. |
| Keywords: | NEURONAL CELL-DEATH, MICROGLIAL ACTIVATION, ALZHEIMERS-DISEASE, MATRIX METALLOPROTEINASES, DOPAMINERGIC-NEURONS, HUMAN PLASMA, MODEL, PROTEIN, PATHOGENESIS, MUTATION |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences > Structural and Molecular Biology |
| URI: | https://discovery.ucl.ac.uk/id/eprint/339613 |
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