English   español  
Please use this identifier to cite or link to this item: http://hdl.handle.net/10261/188120
Share/Impact:
Statistics
logo share SHARE logo core CORE   Add this article to your Mendeley library MendeleyBASE

Visualizar otros formatos: MARC | Dublin Core | RDF | ORE | MODS | METS | DIDL
Exportar a otros formatos:

Title

Cx3cr1‐deficiency exacerbates alpha‐synuclein‐A53T induced neuroinflammation and neurodegeneration in a mouse model of Parkinson's disease

AuthorsCastro-Sánchez, Sara; García-Yagüe, Ángel Juan; López-Royo, Teresa; Casarejos, Maria; Lanciego, José Luis; Lastres-Becker, Isabel
KeywordsCX3CL1
NF-κB
NRF2
Inflammation
Microglia
Pro-inflammarory cytokines
Issue Date2018
PublisherWiley-Liss
CitationGlia 66(8): 1752-1762 (2018)
AbstractParkinson's disease (PD) is the second most common neurodegenerative disorder characterized by the degeneration of dopaminergic neurons of the substantia nigra and the accumulation of protein aggregates, called Lewy bodies, where the most abundant is alpha-synuclein (α-SYN). Mutations of the gene that codes for α-SYN (SNCA), such as the A53T mutation, and duplications of the gene generate cases of PD with autosomal dominant inheritance. As a result of the association of inflammation with the neurodegeneration of PD, we analyzed whether overexpression of wild-type α-SYN (α-SYNWT ) or mutated α-SYN (α-SYNA53T ) are involved in the neuronal dopaminergic loss and inflammation process, along with the role of the chemokine fractalkine (CX3CL1) and its receptor (CX3CR1). We generated in vivo murine models overexpressing human α-SYNWT or α-SYNA53T in wild type (Cx3cr1+/+ ) or deficient (Cx3cr1-/- ) mice for CX3CR1 using unilateral intracerebral injection of adeno-associated viral vectors. No changes in CX3CL1 levels were observed by immunofluorescence or analysis by qRT-PCR in this model. Interestingly, the expression α-SYNWT induced dopaminergic neuronal death to a similar degree in both genotypes. However, the expression of α-SYNA53T produced an exacerbated neurodegeneration, enhanced in the Cx3cr1-/- mice. This neurodegeneration was accompanied by an increase in neuroinflammation and microgliosis as well as the production of pro-inflammatory markers, which were exacerbated in Cx3cr1-/- mice overexpressing α-SYNA53T. Furthermore, we observed that in primary microglia CX3CR1 was a critical factor in the modulation of microglial dynamics in response to α-SYNWT or α-SYNA53T. Altogether, our study reveals that CX3CR1 plays an essential role in neuroinflammation induced by α-SYNA53T.
Publisher version (URL)https://doi.org/10.1002/glia.23338
URIhttp://hdl.handle.net/10261/188120
DOI10.1002/glia.23338
ISSN0894-1491
E-ISSN1098-1136
Appears in Collections:(IIBM) Artículos
Files in This Item:
File Description SizeFormat 
accesoRestringido.pdf59,24 kBAdobe PDFThumbnail
View/Open
Show full item record
Review this work
 

Related articles:


WARNING: Items in Digital.CSIC are protected by copyright, with all rights reserved, unless otherwise indicated.