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Abstract: The inhibition of fibril formation of amyloid β (Aβ) and the disaggregation of Aβ fibrils are the promising approaches for a medical treatment of Alzheimer''s disease (AD) therapy. In this study, we investigated the effects of liposomes on dopamine-induced disaggregation of Aβ fibrils by using the variety of liposomes. The used liposomes were normal liposomes, raft-forming liposomes, charged liposomes and oxidized liposomes. Those liposome could accelerate the disaggregation rate of fibrils. From the comparison of normal and charged liposomes, a certain contribution of dopamine via an electrostatic interaction to the disaggregation was confirmed. From raft-forming and oxidized liposomes, we revealed a significant contribution of bound water to liposomes, which could assist the formation of the quinine-form of dopamine by a removal of its proton. It is, therefore, concluded that the membrane surface of liposomes is considered to be an adequate environment for the dopamine-induced disaggregation of fibrils. [Copyright &y& Elsevier]

Abstract: Alzheimer’s disease is the most common form of senile dementia. This neurodegenerative disorder is characterized by an amyloid deposition in senile plaques, composed primarily of fibrils of an aggregated peptide, amyloid β (Aβ). The modeling of a senile plaque formation on a model neuronal membrane under the physiological condition is an attractive issue. In this study, we used anionic liposomes to model the senile plaque formation by Aβ. The growth behavior of amyloid Aβ fibrils was directly observed, revealing that the induction of the spherulitic Aβ aggregates could result from the growth of seeds in the presence of anionic liposomes. The seeds of Aβ fibrils strongly interacted with negatively charged liposome and the subsequent association of the seeds were induced to form the seed cluster with many growth ends, which is advantageous for the formation of spherulitic Aβ aggregates. Therefore, anionic liposomes mediated not only fibril growth but also the aggregation process. These results imply that anionic liposome membranes would affect the aggregate form of Aβ fibrils. The modeling of senile plaque reported here is considered to have great potential for study on the amyloidosis. [Copyright &y& Elsevier]

ABSTRACT: Amyloid β protein (Aβ) from Alzheimer''s disease formed fibrillar aggregates and their morphology depended on oxidized and negatively charged liposomes. The morphology of fibrillar aggregates was affected by Cu2+, together with their growth kinetics. This is because Cu2+ inhibited the nucleation step in the formation of amyloid Aβ fibrillar aggregates by forming Aβ/Cu complex inactive to the growth of fibrillar aggregates. In addition, this is probably because Cu2+ affected the fibrillar aggregate formed on the surface of liposomes. These findings would give a better understanding of the formation mechanism of amyloid fibrils on biomembranes. [Copyright &y& Elsevier]

Abstract: The inhibition of fibril formation of amyloid β proteins (Aβ) would be attractive therapeutic targets for the treatment of Alzheimer''s disease (AD). Dopamine (DA) and other catechol derivatives were used as inhibitory factors for Aβ fibril formation. The fibril formation of Aβ was monitored by Thioflavin T fluorescence, a transmission electron microscopy (TEM) and a total internal reflection fluorescence microscopy (TIRFM). Catechol and its derivatives showed the dose-dependent inhibitory effects on the spontaneous Aβ fibril formation. The inhibitory activity depended on the chemical structure of catechol derivatives both in the presence and absence of the liposome a model of biomembrane. Formation of catechol quinone-conjugated-Aβ adduct by a Schiff-base is a key step for the inhibition effect of Aβ fibril formation. [Copyright &y& Elsevier]

Abstract: The effective production and secretion of chitosanase from S. griseus cells, in the presence of hydrogen peroxide, were studied by the treatment of the cells with 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphatidylcholine (POPC) liposomes under heat condition. The variation of the conformation and activity of the chitosanase caused by the interaction of liposomes with target chitosanase under stress condition was systematically investigated by using circular dichroism (CD) spectra and dielectric dispersion analysis (DDA). The effect of the oxidative stress (hydrogen peroxide) on the lipid and protein peroxide of cell membrane of S. griseus pretreated with and without liposomes under heat stress at 41 °C was further carried out. The possible utilization of membrane–membrane interaction between liposomes and cell membrane induced by the heat treatment was further investigated to enhance the production of chitosanase from S. griseus under oxidative stress condition. [Copyright &y& Elsevier]