Accumulation of the amyloid protein (Ab) in the brain is an important step in the pathogenesis of Alzheimer's disease. However, the mechanism by which Ab exerts its neurotoxic effect is largely unknown. It has been suggested that the peptide can bind to the a7 nicotinic acetylcholine receptor (a7nAChR). In this study, we examined the binding of Ab1-42 to endogenous and recombinantly expressed a7nAChRs. Ab1-42 did neither inhibit the specific binding of a7nAChR ligands to rat brain homogenate or slice preparations, nor did it influence the activity of a7nAChRs expressed in Xenopus oocytes. Similarly, Ab1-42 did not compete for a-bungarotoxin-binding sites on SH-SY5Y cells stably expressing a7nAChRs. The effect of the Ab1-42 on tau phosphorylation was also examined. Although Ab1-42 altered tau phosphorylation in a7nAChR-transfected SH-SY5Y cells, the effect of the peptide was unrelated to a7nAChR expression or activity. Binding studies using surface plasmon resonance indicated that the majority of the Ab bound to membrane lipid, rather than to a protein component. Fluorescence anisotropy experiments indicated that Ab may disrupt membrane lipid structure or fluidity. We conclude that the effects of Ab are unlikely to be mediated by direct binding to the a7nAChR. Instead, we speculate that Ab may exert its effects by altering the packing of lipids within the plasma membrane, which could, in turn, influence the function of a variety of receptors and channels on the cell surface.

Sulfur mustard is an alkylating agent that reacts with ocular, respiratory, cutaneous, and bone marrow tissues. Main late respiratory complications are chronic obstructive pulmonary disease, bronchiectasis, asthma, and bronchiolitis obliterans. The aim of the present study was to identify differentially expressed proteins in bronchoalveolar lavage (BAL) fluid of control healthy and sulfur mustard-exposed lung disease patients. The BAL protein profile of ten healthy and 30 exposed patients with mild, moderate, and severe conditions (ten males in each group) were separated with 2-D SDS-PAGE and differentially expressed protein spots were successfully identified with MALDI TOF TOF MS. Among the differentially expressed proteins we observed a significant increase in vitamin D binding protein isoforms, haptoglobin isoforms, and fibrinogen especially in exposed moderate and severe lung diseases patients (p<0.01). Moreover, compared with healthy controls, significant decreases was noted in calcyphosine, surfactant protein A, and transthyretin in these patients (p<0.01). Apolipoprotein A1 was detected in all patients' BAL fluid but none of the healthy controls. Furthermore, S100 calcium-binding protein A8 was only detected in BAL fluid of moderate and severe groups. These findings will be useful to improve current methods of monitoring and helps to identify new therapeutic targets for treatment of this complicated illness.

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IntroductionSulfur mustard "bis (2-chlroethyl) sulphide" (SM) is a chemical warfare agent that remains a threat to human health. The aim of this study was to identify protein expression signature or biomarkers that reflect chronic lung damages induced by SM exposure.MethodsPrior to analysis, plasma was fractionated using ethanol precipitation. Using two dimensional SDS-PAGE; fractionated protein profiles of 20 healthy and 20 exposed patients with lung diseases were established. Selected protein spots were successfully identified with MALDI TOF MS/MS.ResultsThe results show that α1 haptoglobin isoforms were detected in plasma of the all lung disease patients but none of the healthy controls. Amyloid A1 isoforms was also detected in plasma of the lung disease patients but none of the healthy controls. Moreover, low molecular weight proteins were enriched in ethanol supernatant compared to ethanol precipitate.ConclusionOur present results and previous studies suggest that ongoing tissue remodeling is involved in SM exposed lung damage patients. These finding might improve patient care and suitable therapies.