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Biography

Atsushi Nagai has acquired medical doctor’s license at 1988 and completed his Ph.D. at 1997 from Shimane Medical University and postdoctoral studies at University of British Columbia, Canada. He is currently the professor of Department of Laboratory Medicine at Shimane University Faculty of Medicine. He has published more than 50 papers in reputed journals.

Abstract

Amyloidβ (Aβ), a 39 to 42 amino acid long peptide derives from amyloid precursor protein, is deposited as fibrils in Alzheimer’s disease (AD) brains and considered as main cause of the disease. We have investigated the effects of a water-soluble Zn-phthalocyanine [ZnPc(COONa)8], which have near infrared optical property, on in vitro Aβ fibril formation process. The ThT fluorescence assay demonstrated that ZnPc(COONa)8 significantly inhibited Aβ fibril formation, as evident by increasing the lag time and dose-dependently decreasing the fibril levels at the plateau. Moreover, it increased the destabilization of the preformed Aβ fibrils and consequently increased monomer, dimer and trimer species of Aβ1-40 in a dose-dependent manner. Immunoprecipitation using Aβ-specific antibody followed by near infrared scanning demonstrated the binding of ZnPc(COONa)8 to Aβ1-42. As a result, the hydrophobicity of the Aβ1-42 fibril formation microenvironment was decreased. Further, SDS-PAGE and dot blot immunoassay showed that ZnPc(COONa)8 delayed the reduction of low molecular weight and appearance of higher molecular weight oligomer species of Aβ1-42. The toxicity of ZnPc(COONa)8 on the culture of a neuronal cell line (A1) was evaluated by MTT cell viability assay. The result showed, that ZnPc(COONa)8 did not decreased the viability, rather protected A1 cells from Aβ1-42-induced toxicity. Thus our results demonstrated that ZnPc(COONa)8 bound to Aβ and decreased the hydrophobicity of fibril formation microenvironment. This change of microenvironment consequently inhibited oligomer and fibril formation process.

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