@article {3624, title = {NLRP3 polymorphism is associated with protection against human T-lymphotropic virus 1 infection.}, journal = {Mem Inst Oswaldo Cruz}, volume = {109}, year = {2014}, month = {2014 Nov}, pages = {960-3}, abstract = {

Inter-individual heterogeneity in the response to human T-lymphotropic virus 1 (HTLV-1) infection has been partially attributed to host genetic background. The antiviral activity of the inflammasome cytoplasmic complex recognises viral molecular patterns and regulates immune responses via the activation of interleukin (IL)-1 family (IL-1, IL-18 and IL-33) members. The association between polymorphisms in the inflammasome receptors NLRP1 and NLRP3 and HTLV-1 infection was evaluated in a northeastern Brazilian population (84 HTLV-1 carriers and 155 healthy controls). NLRP3 rs10754558 G/G was associated with protection against HTLV-1 infection (p = 0.012; odds ratio = 0.37). rs10754558 affects NLRP3 mRNA stability; therefore, our results suggest that higher NLRP3 expression may augment first-line defences, leading to the effective protection against HTLV-1 infection.

}, keywords = {Adult, Brazil, Carrier Proteins, Female, Genetic Predisposition to Disease, HTLV-I Infections, Human T-lymphotropic virus 1, Humans, Inflammasomes, Interleukin-1, Male, Middle Aged, Polymorphism, Single Nucleotide, Protective Factors}, issn = {1678-8060}, author = {Kamada, Anselmo Jiro and Pontillo, Alessandra and Guimar{\~a}es, Rafael Lima and Loureiro, Paula and Crovella, Sergio and Brand{\~a}o, Lucas Andr{\'e} Cavalcanti} } @article {1731, title = {NALP1/NLRP1 genetic variants are associated with Alzheimer disease.}, journal = {Alzheimer Dis Assoc Disord}, volume = {26}, year = {2012}, month = {2012 Jul-Sep}, pages = {277-81}, abstract = {

Alzheimer disease (AD) is a complex neurodegenerative disease. Genetic and molecular studies have confirmed that in the human brain, amyloid-β fibrils can induce, through the activation of NALP1 inflammosome, inflammatory and apoptotic responses involved in the pathogenesis of AD. Considering that AD pathogenesis is multifactorial, we hypothesized that NALP1/NLRP1 could be a susceptibility gene involved in the devolvement of the disease. The possible association between 9 selected polymorphisms in the NALP1/NLRP1 gene and AD was evaluated by comparing their frequency distribution in an Italian cohort of AD patients (AD, n = 276) and in a group of Italian sex-matched and age-matched healthy controls without dementia (HC, n = 266). Our study, evidences the association of 4 nonsynonymous polymorphisms in the NLRP1 gene (rs2137722, rs34733791, rs11657747, rs11651595) with AD. The major alleles of all 4 single nucleotide polymorphisms and the corresponding homozygote genotypes were more frequent in AD patients than in healthy controls, suggesting an association of these variants in the predisposition versus the development of the disease. These findings seem to support the previously reported role of NALP1 in neuronal damage, and provide evidence of an association between single nucleotide variations in the NLRP1 gene and AD.

}, keywords = {Adaptor Proteins, Signal Transducing, Aged, 80 and over, Alzheimer Disease, Apoptosis Regulatory Proteins, Female, Genetic Predisposition to Disease, Genotype, Humans, Italy, Male, Polymerase Chain Reaction, Polymorphism, Single Nucleotide}, issn = {1546-4156}, doi = {10.1097/WAD.0b013e318231a8ac}, author = {Pontillo, Alessandra and Catamo, Eulalia and Arosio, Beatrice and Mari, Daniela and Crovella, Sergio} } @article {1674, title = {Natural isoprenoids inhibit LPS-induced-production of cytokines and nitric oxide in aminobisphosphonate-treated monocytes.}, journal = {Int Immunopharmacol}, volume = {10}, year = {2010}, month = {2010 Jun}, pages = {639-42}, abstract = {

The inhibition of mevalonate pathway through genetic defects (mevalonate kinase deficiency, MKD) or pharmacologic drugs (aminobisphosphonates) causes a shortage of intermediate compounds and, in particular, of geranylgeranyl-pyrophosphate (GGPP) associated to the activation of caspase-1 and IL-1beta release. Geraniol (GOH), farnesol (FOH), geranylgeraniol (GGOH) and menthol (MOH), due to their isoprenoid structure, are supposed to enter the mevalonate pathway and to by-pass the biochemical block, reconstituting the pathway. Considering the already known side effects of aminobisphosphonates, and the lack of a specific treatment for MKD, we evaluated the impact of these natural isoprenoids compounds in a RAW cell lines chemically treated with the aminobisphosphonate alendronate, and in monocytes isolated from 2 patients affected by MKD. GOH, FOH, GGOH and MOH were all capable to diminish inflammatory marker levels induced by LPS. These natural isoprenoids could be proposed as novel therapeutic approach for the still orphan drug MKD, but also considered for the evaluation of possible inflammatory side effects of aminobisphosphonates.

}, keywords = {Animals, Cell Line, Cells, Cultured, Child, Child, Preschool, Cytokines, Diphosphonates, Humans, Inflammation, Interleukin-1beta, Lipopolysaccharides, Male, Mevalonate Kinase Deficiency, Mice, Monocytes, Nitric Oxide, Terpenes}, issn = {1878-1705}, doi = {10.1016/j.intimp.2010.03.008}, author = {Marcuzzi, Annalisa and Tommasini, Alberto and Crovella, Sergio and Pontillo, Alessandra} }