RESUMEN

Cross-reactive vaccines recognize common molecular patterns in pathogens and are able to confer broad spectrum protection against different infections. Antigens common to pathogenic bacteria that induce broad immune responses, such as the glyceraldehyde-3-phosphate dehydrogenase (GAPDH) of the genera Listeria, Mycobacterium, or Streptococcus, whose sequences present more than 95% homology at the N-terminal GAPDH1-22 peptide, are putative candidates for universal vaccines. Here, we explore vaccine formulations based on dendritic cells (DC) loaded with two molecular forms of Listeria monocytogenes GAPDH (LM-GAPDH), such as mRNA carriers or recombinant proteins, and compare them with the same molecular forms of three other antigens used in experimental vaccines, listeriolysin O of Listeria monocytogeness, Ag85A of Mycobacterium marinum, and pneumolysin of Streptococcus pneumoniae. DC loaded with LM-GAPDH recombinant proteins proved to be the safest and most immunogenic vaccine vectors, followed by mRNA encoding LM-GAPDH conjugated to lipid carriers. In addition, macrophages lacked sufficient safety as vaccines for all LM-GAPDH molecular forms. The ability of DC loaded with LM-GAPDH recombinant proteins to induce non-specific DC activation explains their adjuvant potency and their capacity to trigger strong CD4+ and CD8+ T cell responses explains their high immunogenicity. Moreover, their capacity to confer protection in vaccinated mice against challenges with L. monocytogenes, M. marinum, or S. pneumoniae validated their efficiency as cross-reactive vaccines. Cross-protection appears to involve the induction of high percentages of GAPDH1-22 specific CD4+ and CD8+ T cells stained for intracellular IFN-γ, and significant levels of peptide-specific antibodies in vaccinated mice. We concluded that DC vaccines loaded with L. monocytogenes GAPDH recombinant proteins are cross-reactive vaccines that seem to be valuable tools in adult vaccination against Listeria, Mycobacterium, and Streptococcus taxonomic groups.

Asunto(s)

Vacunas Bacterianas/inmunología , Gliceraldehído-3-Fosfato Deshidrogenasas/inmunología , Lípidos/inmunología , Listeria/inmunología , Mycobacterium/inmunología , ARN Mensajero/inmunología , Streptococcus/inmunología , Adyuvantes Inmunológicos , Animales , Anticuerpos Antibacterianos/sangre , Antígenos Bacterianos/genética , Antígenos Bacterianos/inmunología , Infecciones Bacterianas/prevención & control , Vacunas Bacterianas/administración & dosificación , Vacunas Bacterianas/genética , Linfocitos T CD4-Positivos/inmunología , Linfocitos T CD8-positivos/inmunología , Protección Cruzada , Reacciones Cruzadas , Células Dendríticas/inmunología , Gliceraldehído-3-Fosfato Deshidrogenasas/genética , Gliceraldehído-3-Fosfato Deshidrogenasas/metabolismo , Interferón gamma/inmunología , Lípidos/química , Listeria/enzimología , Listeria/genética , Ratones , ARN Mensajero/química , Proteínas Recombinantes/genética , Proteínas Recombinantes/inmunología

RESUMEN

BACKGROUND: The Iberian Peninsula stands out as having variable levels of population admixture and isolation, making Spain an interesting setting for studying the genetic architecture of neurodegenerative diseases. OBJECTIVES: To perform the largest PD genome-wide association study restricted to a single country. METHODS: We performed a GWAS for both risk of PD and age at onset in 7,849 Spanish individuals. Further analyses included population-specific risk haplotype assessments, polygenic risk scoring through machine learning, Mendelian randomization of expression, and methylation data to gain insight into disease-associated loci, heritability estimates, genetic correlations, and burden analyses. RESULTS: We identified a novel population-specific genome-wide association study signal at PARK2 associated with age at onset, which was likely dependent on the c.155delA mutation. We replicated four genome-wide independent signals associated with PD risk, including SNCA, LRRK2, KANSL1/MAPT, and HLA-DQB1. A significant trend for smaller risk haplotypes at known loci was found compared to similar studies of non-Spanish origin. Seventeen PD-related genes showed functional consequence by two-sample Mendelian randomization in expression and methylation data sets. Long runs of homozygosity at 28 known genes/loci were found to be enriched in cases versus controls. CONCLUSIONS: Our data demonstrate the utility of the Spanish risk haplotype substructure for future fine-mapping efforts, showing how leveraging unique and diverse population histories can benefit genetic studies of complex diseases. The present study points to PARK2 as a major hallmark of PD etiology in Spain. © 2019 International Parkinson and Movement Disorder Society.

Asunto(s)

Enfermedad de Parkinson/genética , Adulto , Edad de Inicio , Anciano , Anciano de 80 o más Años , Estudios de Casos y Controles , Mapeo Cromosómico , Costo de Enfermedad , Metilación de ADN , Femenino , Predisposición Genética a la Enfermedad/genética , Estudio de Asociación del Genoma Completo , Genotipo , Haplotipos , Humanos , Aprendizaje Automático , Masculino , Persona de Mediana Edad , Herencia Multifactorial , España , Ubiquitina-Proteína Ligasas/genética

RESUMEN

TMEM230 has been associated with autosomal dominant Parkinson's disease (PD). Subsequent studies have remained negative, and none of previous described mutation has been reported anymore. We investigated the implication of this gene in the PD in a population of 703 PD patients and 695 unrelated healthy controls from southern Spain. Thirteen variants were found, twelve of them observed only in controls or in patients and controls, and one (c.190A>G) observed only in one patient. Subsequent analysis of this variant indicates that probably it is not pathogenic. In addition, we found a variation in the 3'-UTR (rs183551373) and related with the miRNA hsa-miR-4299 but it was observed only in healthy controls. Our results suggest that variants in TMEM230 gene are not associated with the development of PD.

Asunto(s)

Proteínas de la Membrana/genética , Enfermedad de Parkinson/genética , Femenino , Estudios de Asociación Genética , Variación Genética , Humanos , Incidencia , Masculino , MicroARNs/genética , Persona de Mediana Edad , Enfermedad de Parkinson/epidemiología , España/epidemiología

RESUMEN

The dual syndrome hypothesis for cognitive impairment in Parkinson's disease (PD) establishes a dichotomy between a frontrostriatal dopamine-mediated syndrome, which leads to executive deficits, and a posterior cortical syndrome, which leads to dementia. Certain genes have been linked to these syndromes although the exact contribution is still controversial. The study's objective was to investigate the role of APOE, MAPT, COMT, SNCA and GBA genes in the dual syndromes. We genotyped APOE (rs429358 and rs7412), MAPT (rs9468), COMT (rs4680) and SNCA (rs356219) risk polymorphisms and sequenced GBA in a cohort of 298 PD patients. The degree of dopaminergic depletion was investigated with [123I]FP-CIT SPECTs and the presence of dementia was ascertained with a long-term review based on established criteria. The association between genetic and imaging parameters was studied with linear regression, and the relationship with dementia onset with Cox regression. We found that APOE2 allele (Pput = 0.002; Pcau = 0.01), the minor allele 'G' in SNCA polymorphism (Pput = 0.02; Pcau = 0.006) and GBA deleterious variants in (Pput = 0.01; Pcau = 0.001) had a detrimental effect on striatal [123I]FP-CIT uptake in PD. Conversely, Met/Met carriers in COMT polymorphism had increased caudate uptake (Pcau = 0.03). The development of dementia was influenced by APOE4 allele (HR = 1.90; P = 0.03) and GBA deleterious variants (HR = 2.44; P = 0.01). Finally, we observed no role of MAPT locus in any of the syndromes. As a conclusion, APOE2, SNCA, COMT and GBA influence frontostriatal dysfunction whereas APOE4 and GBA influence the development of dementia, suggesting a double-edged role of GBA. The dichotomy of the dual syndromes may be driven by a broad dichotomy in these genetic factors.

Asunto(s)

Cuerpo Estriado/fisiopatología , Demencia/fisiopatología , Lóbulo Frontal/fisiopatología , Enfermedad de Parkinson/fisiopatología , Anciano , Demencia/diagnóstico por imagen , Demencia/genética , Femenino , Predisposición Genética a la Enfermedad , Humanos , Masculino , Enfermedad de Parkinson/diagnóstico por imagen , Enfermedad de Parkinson/genética , Polimorfismo Genético , Tomografía Computarizada de Emisión de Fotón Único

Asunto(s)

Infecciones por Actinomycetales , Actinomycetales , Humanos

RESUMEN

Researching genetic factors involved in Parkinson's disease (PD) is crucial to increase our knowledge about the pathophysiology of the disorder. A missense mutation has recently been reported within CHCHD2, a gene newly associated with autosomal dominant PD. Subsequent studies in different ethnic populations have not reached any conclusive result about the role of CHCHD2 in PD. Therefore, the aim of this study was to investigate the implication of this gene for a PD population from southern Spain (including 536 PD patients and 518 unrelated control subjects). We studied all 4 exons of CHCHD2 and their exon-intron boundary regions. Four variants were observed in non-coding regions. No significant differences were observed in the allele frequencies of these variants between patients and controls. Thus, our study suggests that CHCHD2 is probably not involved in the etiopathogenesis of PD in our population.

Asunto(s)

Estudios de Asociación Genética , Proteínas Mitocondriales/genética , Mutación Missense/genética , Enfermedad de Parkinson/genética , Factores de Transcripción/genética , Anciano , Anciano de 80 o más Años , Proteínas de Unión al ADN , Exones/genética , Femenino , Frecuencia de los Genes/genética , Genes Dominantes/genética , Variación Genética/genética , Humanos , Intrones/genética , Masculino , Persona de Mediana Edad , Riesgo , España

RESUMEN

The presence of mutations in glucocerebrosidase (GBA) gene is a known factor increasing the risk of developing Parkinson's disease (PD). Mutations carriers have earlier disease onset and are more likely to develop neuropsychiatric symptoms than other sporadic PD cases. These symptoms have primarily been observed in Parkinson's patients carrying the most common pathogenic mutations L444P and N370S. However, recent findings suggest that other variants across the gene may have a different impact on the phenotype as well as on the disease progression. We aimed to explore the influence of variants across GBA gene on the clinical features and treatment related complications in PD. In this study, we screened the GBA gene in a cohort of 532 well-characterised PD patients and 542 controls from southern Spain. The potential pathogeniticy of the identified variants was assessed using in-silico analysis and subsequently classified as benign or deleterious. As a result, we observed a higher frequency of GBA variants in PD patients (12.2% vs. 7.9% in controls, p = 0.021), earlier mean age at disease onset in GBA variant carriers (50.6 vs. 56.6 years; p = 0.013), as well as more prevalent motor and non-motor symptoms in patients carrying deleterious variants. In addition, we found that dopaminergic motor complications are influenced by both benign and deleterious variants. Our results highlight the fact that the impact on the phenotype highly depends on the potential pathogenicity of the carried variants. Therefore, the course of motor and non-motor symptoms as well as treatment-related motor complications could be influenced by GBA variants.

Asunto(s)

Glucosilceramidasa/genética , Actividad Motora/genética , Mutación , Enfermedad de Parkinson/genética , Enfermedad de Parkinson/fisiopatología , Anciano , Cognición , Discinesias/complicaciones , Exones/genética , Femenino , Alucinaciones/complicaciones , Humanos , Masculino , Persona de Mediana Edad , Análisis Multivariante , Enfermedad de Parkinson/complicaciones , Enfermedad de Parkinson/enzimología

RESUMEN

BACKGROUND: Tuberculosis (TB) control strategies are focused mainly on prevention, early diagnosis, compliance to treatment and contact tracing. The objectives of this study were to explore the frequency and risk factors of recent transmission of clinical isolates of Mycobacterium tuberculosis complex (MTBC) in Cantabria in Northern Spain from 2012 through 2013 and to analyze their clonal complexity for better understanding of the transmission dynamics in a moderate TB incidence setting. METHODS: DNA from 85 out of 87 isolates from bacteriologically confirmed cases of MTBC infection were extracted directly from frozen stocks and genotyped using the mycobacterial interspersed repetitive units-variable number tandem repeat (MIRU-VNTR) method. The MIRU-VNTRplus database tool was used to identify clusters and lineages and to build a neighbor joining (NJ) phylogenetic tree. In addition, data were compared to the SITVIT2 database at the Pasteur Institute of Guadeloupe. RESULTS: The rate of recent transmission was calculated to 24%. Clustering was associated with being Spanish-born. A high prevalence of isolates of the Euro-American lineage was found. In addition, MIRU-VNTR profiles of the studied isolates corresponded to previously found MIRU-VNTR types in other countries, including Spain, Belgium, Great Britain, USA, Croatia, South Africa and The Netherlands. Six of the strains analyzed represented clonal variants. CONCLUSION: Transmission of MTBC is well controlled in Cantabria. The majority of TB patients were born in Spain. The population structure of MTBC in Cantabria has a low diversity of major clonal lineages with the Euro-American lineage predominating.

Asunto(s)

Epidemiología Molecular , Mycobacterium tuberculosis/genética , Tuberculosis/epidemiología , Tuberculosis/genética , Adulto , Femenino , Genotipo , Humanos , Masculino , Persona de Mediana Edad , Repeticiones de Minisatélite/genética , Mycobacterium tuberculosis/patogenicidad , Filogenia , España , Tuberculosis/microbiología

RESUMEN

BACKGROUND: Tourette syndrome is a disorder characterized by persistent motor and vocal tics, and frequently accompanied by the comorbidities attention deficit hyperactivity disorder and obsessive-compulsive disorder. Impaired synaptic neurotransmission has been implicated in its pathogenesis. Our aim was to investigate the association of 28 candidate genes, including genes related to synaptic neurotransmission and neurotrophic factors, with Tourette syndrome. METHODS: We genotyped 506 polymorphisms in a discovery cohort from the United States composed of 112 families and 47 unrelated singletons with Tourette syndrome (201 cases and 253 controls). Genes containing significant polymorphisms were imputed to fine-map the signal(s) to potential causal variants. Allelic analyses in Tourette syndrome cases were performed to check the role in attention deficit hyperactivity disorder and obsessive-compulsive disorder comorbidities. Target polymorphisms were further studied in a replication cohort from southern Spain composed of 37 families and three unrelated singletons (44 cases and 73 controls). RESULTS: The polymorphism rs3096140 in glial cell line-derived neurotrophic factor gene (GDNF) was significant in the discovery cohort after correction (P = 1.5 × 10(-4) ). No linkage disequilibrium was found between rs3096140 and other functional variants in the gene. We selected rs3096140 as target polymorphism, and the association was confirmed in the replication cohort (P = 0.01). No association with any comorbidity was found. CONCLUSIONS: As a conclusion, a common genetic variant in GDNF is associated with Tourette syndrome. A defect in the production of GDNF could compromise the survival of parvalbumin interneurons, thus altering the excitatory/inhibitory balance in the corticostriatal circuitry. Validation of this variant in other family cohorts is necessary.

Asunto(s)

Estudios de Asociación Genética , Factor Neurotrófico Derivado de la Línea Celular Glial/genética , Transmisión Sináptica/genética , Síndrome de Tourette/genética , Adolescente , Adulto , Niño , Estudios de Cohortes , Femenino , Humanos , Masculino , Persona de Mediana Edad , Linaje , Polimorfismo Genético , Estados Unidos , Adulto Joven

RESUMEN

Recurrent bloodstream infections caused by a Gram-positive bacterium affected an immunocompromised child. Tsukamurella pulmonis was the microorganism identified by secA1 gene sequencing. Antibiotic treatment in combination with removal of the subcutaneous port healed the patient.

Asunto(s)

Actinobacteria/aislamiento & purificación , Infecciones por Bacterias Grampositivas/diagnóstico , Infecciones por Bacterias Grampositivas/patología , Proteínas de Transporte de Membrana/genética , Sepsis/diagnóstico , Sepsis/patología , Actinobacteria/clasificación , Actinobacteria/genética , Antibacterianos/uso terapéutico , Preescolar , ADN Bacteriano/química , ADN Bacteriano/genética , Remoción de Dispositivos , Femenino , Infecciones por Bacterias Grampositivas/microbiología , Humanos , Huésped Inmunocomprometido , Datos de Secuencia Molecular , Infecciones Oportunistas/diagnóstico , Infecciones Oportunistas/microbiología , Infecciones Oportunistas/patología , Recurrencia , Sepsis/microbiología , Análisis de Secuencia de ADN , Resultado del Tratamiento

RESUMEN

BACKGROUND: A recent genome-wide association study (GWAS) has identified a putative association, not statistically confirmed, of cervical dystonia within several regions in a British population. Hence, the authors proposed dysfunction of the ion channel NALCN (for sodium leak channel, nonselective) as a plausible cause of cervical dystonia. The objective of our study was to investigate the association of five single nucleotide polymorphisms (SNPs) previously reported with high signals as putative genetic risk factors for cervical dystonia in a British GWAS, including two located in the NALCN gene region. METHODS: We performed a case-control association study in a Spanish population. The SNPs selected for genotyping were two SNPS in the NALCN gene (rs61973742 and rs1338041), one SNP in the OR4X2 gene (rs67863238), one SNP in the COL4A1 region (rs619152), and one intergenic SNP (rs1249277). Genomic DNA was collected from 252 patients with cervical dystonia, with a mean age of 55.3 ± 14.1 years (mean age at onset, 43.5 ± 15.7 years), and 342 unrelated control subjects with a mean age of 56.3 ± 14.3 years. Genotyping of SNPs was performed using TaqMan assays and SimpleProbe assays. RESULTS: The SNP rs619152 had to be excluded because of assay failure. No significant differences were found in allele distribution between cases and controls for all analyzed SNPs. Therefore, we found no association with cervical dystonia for the analyzed SNPs in our Spanish population. CONCLUSIONS: We did not find any evidence supporting the association of NALCN with cervical dystonia, indicating that this gene is not implicated in the pathogenesis of this disorder in our cervical dystonia population.

Asunto(s)

Distonía/genética , Frecuencia de los Genes/genética , Predisposición Genética a la Enfermedad , Estudio de Asociación del Genoma Completo , Polimorfismo de Nucleótido Simple/genética , Adulto , Edad de Inicio , Anciano , Estudios de Casos y Controles , Femenino , Estudio de Asociación del Genoma Completo/métodos , Genotipo , Humanos , Persona de Mediana Edad , Riesgo , Población Blanca

RESUMEN

BACKGROUND: A polymorphism in brain-derived neurotrophic factor (BDNF) (Val66Met) has been reported as a risk factor in primary dystonia. However, overall the results have been inconclusive. Our aim was to clarify the association of Val66Met with primary dystonia, and with the most prevalent clinical subtypes, cervical dystonia and blepharospasm. METHODS: We conducted a Spanish multicenter case-control study (including 680 primary dystonia patients and 788 healthy controls) and performed a meta-analysis integrating our study and six previously published studies (including a total of 1,936 primary dystonia patients and 2,519 healthy controls). RESULTS: We found no allelic or genotypic association with primary dystonia, cervical dystonia, or blepharospasm risks, for the allele A (Met) from a BDNF Val66Met polymorphism in our case-control study. This was confirmed by results from our meta-analysis in white and mixed ethnic populations in any genetic model. CONCLUSION: We did not find any evidence supporting the association of the BDNF Val66Met polymorphism with primary dystonia.

Asunto(s)

Factor Neurotrófico Derivado del Encéfalo/genética , Trastornos Distónicos/genética , Predisposición Genética a la Enfermedad/genética , Polimorfismo de Nucleótido Simple/genética , Adulto , Anciano , Estudios de Casos y Controles , Femenino , Frecuencia de los Genes , Estudios de Asociación Genética , Genotipo , Humanos , Masculino , Metionina/genética , Persona de Mediana Edad , Valina/genética

RESUMEN

Mutations in FBXO7 (PARK15) have been associated with a syndrome characterized by early-onset progressive parkinsonism with and without pyramidal tract signs. Therefore, our aim was to analyze this gene in a population from southern Spain (338 Parkinson's disease [PD] patients and 330 unrelated control subjects) to elucidate the potential involvement of FBXO7 in PD pathogenesis. We identified 17 variants (11 novel), including 10 missense substitutions, 3 synonymous, and 4 intronic alterations. Six substitutions were described as putatively damaging by the bioinformatics tools and 1 intronic variation was described to affect splicing. Minor allele frequencies of the highly polymorphic coding single nucleotide polymorphisms (SNPs) in PD patients and control subjects were similar. All rare variants were heterozygous. No deletions or duplications involving FBXO7 exons were identified. Our results suggest that the involvement of the FBXO7 gene in PD is very rare, at least in this population from southern Spain.

Asunto(s)

Proteínas F-Box/genética , Mutación , Enfermedad de Parkinson/genética , Edad de Inicio , Análisis Mutacional de ADN/métodos , Humanos , Enfermedad de Parkinson/epidemiología , España/epidemiología

Asunto(s)

Proteínas del Choque Térmico HSP40/genética , Mutación , Enfermedad de Parkinson/genética , Adulto , Edad de Inicio , Anciano , Análisis Mutacional de ADN , Femenino , Predisposición Genética a la Enfermedad , Humanos , Masculino , Persona de Mediana Edad , España

RESUMEN

Parkinson's disease (PD) is a neurodegenerative disease caused by both genetic and environmental factors. Sirtuins are highly-conserved, NAD-dependent class III deacetylases that regulate a variety of cellular functions. Most of the known sirtuins have been involved in animal models of neurodegenerative disorders, such as PD. Although seven sirtuin family members have been identified (SIRT1-SIRT7) the relationship between sirtuins and PD in humans has not been established. Our aim was to investigate the association between sirtuin genes and risk of PD. We included 326 PD patients and 371 controls from southern Spain. Forty-one single nucleotide polymorphisms (SNPs) in sirtuin genes were genotyped in order to determine whether they were related to the risk of PD. These SNPs included Tag-SNPs, coding non-synonymous SNPs and SNPs affecting activity of microRNA binding sites. No relationship was found between these SNPs in sirtuin genes and PD. Our data indicate that variations in sirtuin genes do not affect the risk for PD, at least in our population.

Asunto(s)

Predisposición Genética a la Enfermedad , Enfermedad de Parkinson/genética , Polimorfismo de Nucleótido Simple , Sirtuinas/genética , Predisposición Genética a la Enfermedad/genética , Genotipo , Humanos , Persona de Mediana Edad , Espectrometría de Masa por Láser de Matriz Asistida de Ionización Desorción

RESUMEN

BACKGROUND: Impairment of the ubiquitin-proteasome system has been suggested to play an important role in the pathogenesis of Parkinson's disease (PD). The 26S proteasome regulatory subunit 1 is encoded by the gene PSMC1 in humans. PSMC1 knockout mice showed a PD-like phenotype. Our aim was to analyze the association between variations in this gene and the susceptibility to develop PD. METHODS: We included 283 PD patients (165 males and 118 females) with a mean age of 63.6±11.2 years (mean age at onset 55.4±12.7 years), and 316 unrelated control subjects (193 males and 123 females) with a mean age of 61.5±12.3 years. Four polymorphisms, providing haplotype information of PSMC1, were genotyped using TaqMan assays. Moreover, in order to identify new variations, all exons of the PSMC1 gene and their exon-intron boundaries were analyzed using high-resolution melting analysis. RESULTS: Minor allele frequencies in PD patients and control subjects were similar. The gene coding sequence analysis showed no variation associated with the disease either. CONCLUSIONS: Our results suggest that there is no association between variations or haplotypes in the PSMC1 gene and PD, indicating that this gene is probably not involved in the pathogenesis of PD.

Asunto(s)

Adenosina Trifosfatasas/genética , Predisposición Genética a la Enfermedad/genética , Enfermedad de Parkinson/genética , Complejo de la Endopetidasa Proteasomal/genética , ATPasas Asociadas con Actividades Celulares Diversas , Anciano , Femenino , Frecuencia de los Genes , Genotipo , Haplotipos , Humanos , Masculino , Persona de Mediana Edad , Polimorfismo de Nucleótido Simple

RESUMEN

Acinetobacter junii is a rare human pathogen associated with bacteraemia in neonates and paediatric oncology patients. We present a case of A. junii causing bacteraemia in an adult transplant patient with leukaemia. The correct identification of Acinetobacter species can highlight the clinical significance of the different species of this genus.

Asunto(s)

Infecciones por Acinetobacter/diagnóstico , Acinetobacter/aislamiento & purificación , Bacteriemia/diagnóstico , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Leucemia-Linfoma Linfoblástico de Células Precursoras/complicaciones , Acinetobacter/efectos de los fármacos , Acinetobacter/genética , Infecciones por Acinetobacter/microbiología , Adulto , Antibacterianos/farmacología , Bacteriemia/microbiología , Técnicas de Tipificación Bacteriana , Dermatoglifia del ADN , Femenino , Humanos , Pruebas de Sensibilidad Microbiana , Tipificación Molecular , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia

RESUMEN

The cause of Parkinson's disease remains unknown although some evidence suggests that an inflammatory reaction, mediated by cytokines such as TNF-alpha and IL-1beta, is related with dopaminergic degeneration in the brain. In the present work we measured the plasma levels of TNF-alpha and IL-1beta in parkinsonian monkeys one year after MPTP administration. TNF-alpha levels were seen to have increased in parkinsonian monkeys reflecting the clinical symptoms observed, while IL-1beta levels remained unchanged. These results suggest that TNF-alpha plays a role in sustaining of dopaminergic degeneration in chronic parkinsonism.

Asunto(s)

Interleucina-1/sangre , Trastornos Parkinsonianos/inmunología , Factor de Necrosis Tumoral alfa/metabolismo , 1-Metil-4-fenil-1,2,3,6-Tetrahidropiridina/farmacología , Animales , Dopamina/fisiología , Macaca fascicularis , Masculino , Degeneración Nerviosa/sangre , Degeneración Nerviosa/inmunología , Neurotoxinas/farmacología , Trastornos Parkinsonianos/sangre