Lipopolysaccharides (LPS) isolated from Bordetella pertussis (Bp), B. parapertussis (Bpp), and B. bronchiseptica (Bbs) were analysed for their chemical composition, molecular heterogeneity, and immunological and biological properties. All LPS contained heptose, KDO, GlcN, uronic acid, phosphate, and fatty acids. The fatty acids C14:0, C16:0 and 3-OHC14:0 were common to all LPS preparations. By SDS-PAGE, Bp-LPS had two bands of low molecular mass, and Bpp- and Bbs-LPS showed a low molecular mass band together with ladder bands of high molecular mass. Immunological assays demonstrated that Bp-LPS reacted with antisera prepared from Bp and Bpp; Bpp-LPS reacted with antisera against Bpp and Bbs, and Bbs-LPS reacted with antisera against any of the three species. Bp-LPS showed biological activities comparable to those of E. coli LPS in terms of lethal toxicity, pyrogenicity, mitogenicity, macrophage activation, and induction of tumor necrosis factor. All activities of Bpp-LPS, except mitogenicity, were lower than those of E. coli LPS. Biological activities stronger or comparable to those of E. coli LPS were observed for Bbs-LPS.
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Background: Small, soluble oligomers, rather than mature fibrils, are the major neurotoxic agents in Alzheimer's disease (AD). In the last few years, Aprile and co-workers designed and purified a single-domain antibody (sdAb), called DesAb-O, with high specificity for Aβ oligomeric conformers. Recently, Cascella and co-workers showed that DesAb-O can selectively detect synthetic Aβ oligomers both in vitro and in cultured cells, neutralizing their associated neuronal dysfunction.
View Article and Find Full Text PDFAlzheimers Dement
December 2024
Indiana University School of Medicine, Indianapolis, IN, USA.
Background: The goal of the TREAT-AD Center is to enable drug discovery by developing assays and providing tool compounds for novel and emerging targets. The role of microglia in neuroinflammation has been implicated in the pathogenesis of Alzheimer's disease (AD). Genome-wide association studies, whole genome sequencing, and gene-expression network analyses comparing normal to AD brain have identified risk and protective variants in genes essential to microglial function.
View Article and Find Full Text PDFBackground: A large body of evidence now indicates that the most pathogenic species of Aß in Alzheimer's disease (AD) consist of soluble toxic oligomers (AßO) as opposed to insoluble fibrils and monomers. Using our computational platform, we identified 4 different AßO-restricted conformational B cell epitopes (300, 301, 303, 305) that were tested as vaccines for their ability to induce an antibody response that selectively targets toxic AßO, without inducing potentially detrimental B or T cell responses against plaque or normal Aß. A novel ex vivo approach was then used to select an optimal vaccine configuration amongst the 15 possible combinations of the 4 epitopes to provide maximal binding to a toxic oligomer-enriched low molecular weight (LMW) fraction of soluble AD brain extracts.
View Article and Find Full Text PDFAlzheimer's disease pathophysiology is believed to involve various abnormalities, including those of amyloid beta (Ab) peptide and tau processing, inflammation, oxidative stress, and vascular risk factors. Aβ peptides exist in a dynamic continuum of conformational states from monomeric Aβ, to soluble progressively larger Aβ assemblies that include a range of low molecular weight oligomers to higher molecular weight protofibrils, and finally to insoluble fibrils (plaques). Various lines of evidence support the "amyloid hypothesis" that Aβ plays a central role in the pathogenesis of AD, and several immunotherapies have been developed to interact with this cascade in various different places which may reduce the number of soluble aggregates and insoluble Aβ fibrils deposited in the brain.
View Article and Find Full Text PDFAlzheimers Dement
December 2024
UIPS, CHANDIGARH, Punjab, India.
Background: Alzheimer's disease is a brain disorder that causes neurodegeneration and is linked with insulin resistance at molecular, clinical, and demographic levels. Defective insulin signaling promotes Aβ aggregation and accelerates Aβ formation in the brain leading to Type III diabetes.
Objective: The objective of this research project is to demonstrate a linkage if any between the risk of developing Alzheimer's disease and insulin resistance.
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