Chemokines (RANTES and MCP-1) and chemokine-receptors (CCR2 and CCR5) gene polymorphisms in Alzheimer's and Parkinson's disease

Huerta, Cecilia; Álvarez, Victoria; Mata, Ignacio; Coto, Eliécer; Ribacoba, René; Martı́nez, Carmen; Blázquez, Marta; Guisasola, Luis M.; Salvador, Carlos; Lahoz, Carlos H.; Peña, Joaquín

doi:10.1016/j.neulet.2004.08.016

Cited by 64 publications

(45 citation statements)

References 26 publications

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“…Mcp-1/ Ccl2 and its receptor have been implicated in several models of neurodegeneration (Bruno et al, 2000,Muessel et al, 2000,Siebert et al, 2000,Eugenin et al, 2003,Kalehua et al, 2004 including retrograde degeneration (Ghirnikar et al, 2001,Muessel et al, 2002,Perrin et al, 2005. In addition, although controversial, polymorphisms in the Mcp-1/Ccl2 promoter have been linked to sporadic PD (Nishimura et al, 2003,Huerta et al, 2004. We have confirmed that Mcp-1/Ccl2 is induced in striatum after MPTP administration (Sriram et al, 2006b).…”

supporting

confidence: 65%

“…Moreover elevated levels of cytokines such as tumor necrosis factor alpha (Tnf-α), interleukin 6 (Il-6), interleukin 1 beta and interferon gamma (Ifn-γ) have been observed in the SNpc of PD patients and rodents treated with 6-OHDA and MPTP ,Nagatsu et al, 2000,Nagatsu and Sawada, 2005,Sriram et al, 2006b. Therefore, these molecules may be actively involved in disease progression.Several studies also sought to correlate polymorphisms in the promoters of several cytokine genes to the risk of developing PD (Nishimura et al, 2000,Schulte et al, 2002,Nishimura et al, 2003,Huerta et al, 2004,Ross et al, 2004,Hakansson et al, 2005. Furthermore, retrospective clinical studies in populations subjected to chronic use of non steroidal antiinflammatory drugs (NSAIDs) suggest that some of these agents could lower the incidence of PD (Chen et al, 2003,Schiess, 2003,Hernan et al, 2006.…”

mentioning

confidence: 99%

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Temporal mRNA profiles of inflammatory mediators in the murine 1-methyl-4-phenyl-1,2,3,6-tetrahydropyrimidine model of Parkinson’s disease

2007

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Parkinson's disease (PD) is a neurodegenerative disorder characterized by the loss of dopaminergic neurons in the substantia nigra pars compacta (SNpc). With the exception of a few rare familial forms of the disease, the precise molecular mechanisms underlying PD are unknown. Inflammation is a common finding in the PD brain, but due to the limitation of postmortem analysis its relationship to disease progression cannot be established. However, studies using the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) model of PD have also identified inflammatory responses in the nigrostriatal pathway that precede neuronal degeneration in the SNpc. To assess the pathological relevance of these inflammatory responses and to identify candidate genes that might contribute to neuronal vulnerability, we used quantitative reverse-transcription polymerase chain reaction (qRT-PCR) to measure mRNA levels of 11 cytokine and chemokine encoding genes in the striatum of MPTP-sensitive (C57BL/6J) and MPTP-insensitive (Swiss Webster, SWR) mice following administration of MPTP. The mRNA levels of all 11 genes changed following MPTP treatment, indicating the presence of inflammatory responses in both strains. Furthermore, of the 11 genes examined only 3, interleukin 6 (Il-6), macrophage inflammatory protein 1 alpha/CC chemokine ligand 3 (Mip-1alpha/Ccl3) and macrophage inflammatory protein 1 beta/CC chemokine ligand 4 (Mip-1beta/Ccl4), were differentially regulated between C57BL/6J and SWR mice. In both mouse strains, the level of monocyte chemoattractant protein 1/CC chemokine ligand 2 (Mcp-1/Ccl2) mRNA was the first to increase following MPTP administration, and might represent a key initiating component of the inflammatory response. Using Mcp-1/Ccl2 knockout mice backcrossed onto a C57BL/6J background we found that MPTP-stimulated Mip-1alpha/Ccl3 and Mip-1beta/Ccl4 mRNA expression was significantly lower in the knockout mice; suggesting that Mcp-1/Ccl2 contributes to MPTP-enhanced expression of Mip-1alpha/Ccl3 and Mip-1beta/Ccl4. However, stereological analysis of SNpc neuronal loss in Mcp-1/Ccl2 knockout and wild-type mice showed no differences. These findings suggest that it is the ability of dopaminergic SNpc neurons to survive an inflammatory insult, rather than genetically determined differences in the inflammatory response itself, that underlie the molecular basis of MPTP resistance.

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confidence: 65%

mentioning

confidence: 99%

Temporal mRNA profiles of inflammatory mediators in the murine 1-methyl-4-phenyl-1,2,3,6-tetrahydropyrimidine model of Parkinson’s disease

2007

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“…In the central nervous system (CNS), chemokine receptors are expressed primarily by microglia, astrocytes, neurons, and endothelial cells [19]. Among chemokines, interleukin-8 is a key mediator associated with inflammation.…”

Section: Discussionmentioning

confidence: 99%

A Case-Control Association Study ofRANTES (-28C>G)Polymorphism as a Risk Factor for Parkinson’s Disease in Isparta, Turkey

Sahin-Calapoglu

Demirci

Calapoğlu

et al. 2016

Parkinson's Disease

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Background. Recent studies have revealed that inflammatory processes are involved in the pathogenesis of Parkinson's disease (PD). Multiple lines of evidence have suggested that chemokines and their receptors are involved in several neurodegenerative disorders. We have examined whether genetic polymorphisms at the genes encoding chemokines IL-8 (-251A>T), MCP-1 (-2518A/G), and RANTES (-28C>G) and chemokine receptors CCR2 (V64I) and CCR5 (-Δ32) were associated with sporadic PD risk in Isparta, Turkey. Method. The pilot case-control association study included 30 PD patients and 60 control subjects, who were all genotyped with PCR-RFLP for the five polymorphisms. Their genotype and haplotype frequencies were compared statistically. Results. One SNP (-28C>G) in RANTES revealed a significant association with PD (P (allele) < 0.0001, p-trend = 0.0007). The risk allele (G) in the homozygous and dominant models (OR = 17.29 and 32.10, 95% CI = 0.86–347.24 and 1.74–591.937, resp.) suggests additional PD risk. The haplotype TGCAN from the IL-8 (-251A>T), MCP-1 (-2518A>G), RANTES (-28C>G), CCR-2 (V64I), and CCR-5 (-Δ32) has protective effect (OR = 0.08 [CI = 0.01–0.63], p = 0.019). Conclusions. Our data are the first indication of the role of RANTES (-28C>G) in PD risk.

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“…A potential variation in IL-8 expression in PD subjects may facilitate the influx of neutrophils, immune and activated glial cells to sites of damage and inflammation, resulting in increased oxidative damage and cell death. However when Huerta and colleagues (2004) examined the frequency of polymorphic variants in four chemokine genes, RANTES , MCP-1 , CCR2 and CCR5 , no significant associations with PD were observed in the Spanish population studied [ 49 ]. These results support earlier results for MCP-1 and CCR2 observed by Nishimura et al in the Japanese population.…”

Section: Pd and Cytokinessupporting

confidence: 53%

Cytokine Polymorphisms and Immunosenescence

Ross

Hinkle

Rea³

Handbook on Immunosenescence

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:The influence of genetics on immunosenescence is still to be resolved. Common genetic variants (polymorphism) that reside within the genes encoding cytokines are candidates to positively or negatively affect immunosenescence. Cytokines regulate the type and magnitude of the immune function. Polymorphism can influence the expression level of the cytokine protein which can subsequently cause an imbalance in the cytokine cascade.Herein we examine the current literature with respect to cytokine polymorphisms in ageing and the age-related neurodegenerative disorder, Parkinson's disease.

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Chemokines (RANTES and MCP-1) and chemokine-receptors (CCR2 and CCR5) gene polymorphisms in Alzheimer's and Parkinson's disease

Cited by 64 publications

References 26 publications

Temporal mRNA profiles of inflammatory mediators in the murine 1-methyl-4-phenyl-1,2,3,6-tetrahydropyrimidine model of Parkinson’s disease

Temporal mRNA profiles of inflammatory mediators in the murine 1-methyl-4-phenyl-1,2,3,6-tetrahydropyrimidine model of Parkinson’s disease

A Case-Control Association Study ofRANTES (-28C>G)Polymorphism as a Risk Factor for Parkinson’s Disease in Isparta, Turkey

Cytokine Polymorphisms and Immunosenescence

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