K Matsuzaki

..Fluorescence experiments revealed that Abeta aggregated in buffer did not show any affinity for membranes...

..This method provides a novel system useful for investigating the dynamic biological functions of Abeta1-42 in AD by inducible activation of Abeta1-42 self-assembly...

..A novel mode of action is discussed in detail, i.e., the formation of a dynamic peptide-lipid supramolecular pore, which allows the mutually coupled transbilayer transport of ions, lipids, and peptides per se...

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..The peptide molecule is internalized upon the disintegration of the pore. Several anti-microbial peptides are known to work synergistically...

..Furthermore, nordihydroguaiaretic acid was found to effectively inhibit the ganglioside-induced amyloidogenesis by preventing the binding of Abeta to the membrane...

..Thus, our helical Abeta1-42 is not only a model peptide to investigate the role of helical intermediates in fibrillization by Abeta, but also an inhibitor of Abeta-induced cytotoxicity...

..Pros and cons of these approaches are discussed...

..The importance of ganglioside clusters in the aggregation of Abeta is emphasized. Finally, a hypothetical physicochemical cascade in the pathogenesis of the disease is proposed...

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..This system seems to be useful for investigating the molecular details of peptide-lipopolysaccharide interactions...

..The charge distribution of wild-type magainin 2 was found to be so designed as to exhibit the maximal lytic activity by simultaneously achieving a strong binding and a moderate pore stability...

..Substitution of Trp for Phe simultaneously increased the bactericidal activity and the hemolytic activity. A strategy to develop potent antimicrobial peptides was discussed on the basis of these results...

..A novel model for the melittin pore formation was discussed in comparison with other pore-forming peptides...

..These results suggest that the peptide imposes positive curvature strain, facilitating the formation of a torus-type pore, and that the presence of negative curvature-inducing lipids inhibits pore formation...

..Therefore, the synergism is a consequence of the formation of a potent heterosupramolecular complex, which is characterized by fast pore formation and moderate pore stability...

..Furthermore, a comparison of the inhibitory effects of various compounds between aqueous-phase and GM1-mediated aggregation of Abeta suggested that the two aggregation processes are not identical...

..These results suggest that Abeta (1-40) imposes negative curvature strain on ganglioside-containing lipid bilayers, disturbing the structure and function of the membranes...

..A simple theoretical calculation could explain the coupling of the flip-flop with the permeabilization...

..These novel observations suggested the possibility of the development of cocktail therapeutic regimens using combinations of antimicrobial peptides...

..A novel model of the mastoparan-lipid interactions was proposed to explain these observations...

..The results of the present study strongly suggested that increases in intramembrane cholesterol content, which are likely to occur during aging, appear to be a risk factor for amyloid fibril formation...

..This study suggests that toxic Abeta(1-40) species formed on membranes are not soluble oligomers but amyloid fibrils and that Abeta(1-40) fibrils exhibit polymorphisms...

..Our system using NGF-differentiated PC12 cells and Congo red is useful for screening inhibitors of the formation of amyloids by and cytotoxicity of Abeta...

..GM1-Abeta exhibited the strongest seeding potential, especially under beta-sheet-forming conditions. This study suggested that lipid composition including gangliosides and cholesterol strictly controls amyloid formation...

..Our study suggests an exacerbation mechanism of AD and an importance of polymorphisms in Abeta fibrils during the pathogenesis of the disease...

..These results suggest that the lipid raft containing a ganglioside cluster serves as a conformational catalyst or a chaperon generating a membrane-active form of A beta with seeding ability...

..Vitality increased significantly only in those patients with the greatest increases in Hb concentration and in those with higher final Hb concentrations...

..In addition, CHPNH(2) nanogels protected PC12 cells from Abeta toxicity...

..The depletion of gangliosides or cholesterol significantly reduced the amount of amyloid deposited. These results clearly showed that the formation of amyloid fibrils was mediated by gangliosides in lipid rafts...

..Cholesterol depletion significantly reduced Abeta accumulation. These observations corroborate the GM1-mediated Abeta accumulation model...

..This click peptide strategy should provide a reliable experimental system to investigate the pathological role of Abeta1-42 in Alzheimer's disease...

..The results emphasize the importance of the conformational flexibility of the Abeta molecule and a balance in the association and dissociation rate for the formation of rigid amyloid fibrils...

..The presence of Pro(11) distorts the helix, concentrating basic amino acid residues in a limited amphipathic region, thus destabilizing the pore by enhanced electrostatic repulsion, enabling efficient translocation...

..Furthermore, a reduction in DNA binding by PEGylation may also contribute to the weak activity of the PEGylated peptide...

..These observations demonstrate that the hydrophobicity of the peptide also controls the mode of action and is dependent on the position of the hydrophobic amino acids in the peptide sequence...

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..These results suggested that hydrogen-bonding as well as hydrophobic interactions with sugar groups of glycolipids drive the membrane binding of Abeta-(1-40)...

..In this review, we focus on the recent progress of GAbeta studies and highlight the possibility that ganglioside binding is the initial and common step in the development of a part of human misfolding-type amyloidoses, including AD...

..Electron spin resonance spectra of 1-palmitoyl-2-stearoyl-(14-doxyl)-sn-glycero-3-phosphocholine demonstrated the presence of a motionally restricted component at lower temperatures...

..On the basis of these observations, a model for the helix insertion/dissociation processes was discussed...

..However, the mechanism appeared to be different from that of the parent peptide...

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..CONCLUSIONS: Both genetic variants and glycan structures significantly contribute to the enantioselectivity and the binding affinity of OXY...

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..The new concept of dipole-dipole interaction as a basic driving force of helix dimerization will become a basis for understanding the structural and functional modifications in response to hydrophobic mismatch...

..6 kJ mol(-1). Thus, the transmembrane helix was found to be a useful template for thermodynamic measurements of the partitioning of amino acids from water to the hydrophobic core of membranes...

..Thus, the distinct membrane-permeabilizing processes of magainin 2 in bacterial and mammalian cells were, to the best of our knowledge, visualized and characterized in detail for the first time...

..At the same time, the antimicrobial activity was weakened only by 4 fold. The effects of PEGylation on the activity of magainin were compared with those for tachyplesin...

..The CV% values of intra-day and inter-day assays (n=15) were less than 14.9% for T4, 14.5% for T3 and 13.2% for rT3. The present system was also applied to a competitive binding study of these thyroid hormones in human plasma...

..These results demonstrate for the first time specific interaction between the intracellular third loop and the C-terminus. A model is proposed for the activation of the receptor...

..Thus, the separate production of mutually recognizing peptides without cross-linking appears to be a good way to increase selective toxicity...

..These results suggest that there are favorable local environments for fibrillogenesis of amyloid beta-protein...

..These results suggest that cinnamycin promotes its own binding to the cell and causes toxicity by inducing transbilayer lipid movement...

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..These results imply a mechanism underlying the onset of AD and suggest that an endogenous seed can be a target of therapeutic strategy...

..Our data suggest a mechanism by which elevated Abeta1-42/Abeta1-40 ratio accelerates the development of Alzheimer's disease (AD) in familial AD...

..The results of our current studies may provide a new insight into the molecular mechanism underlying the cholesterol-dependent development of AD...

..This study suggests that cross-seeding can occur between wild and hereditary variant-type amyloid beta-proteins despite differences in their amino acid sequences...

..The recognition site was the lipid A moiety and the cyclic structure was crucial to this specific binding. The cyclic structure also endowed the peptide with very rapid outer membrane (OM) permeabilization...