ハイブリッドリポソームを用いたアルツハイマー病治療に関する基礎研究

概要

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Accumulation of β amyloid (Aβ) peptides to nerve cells should be associated with the onset of Alzheimers disease (AD). We prepared hybrid liposomes (HL) composed of 90 mol% phospholipids having various charged head groups (cationic L-α-dimyristoyltrimethyl ammonium propane (DMTAP), anionic L-α-dimyristoylphosphatidylserine (DMPS) or zwitterionic L-α-dimyristoylphosphatidylcholine (DMPC)) and 10 mol% polyoxyethylene(23) dodecyl ether (C12(EO)23)), and investigated the inhibitory effects of HL on the accumulation of Aβ1-40 peptides into human neuroblastoma (SH-SY5Y) cells in vitro. It is noteworthy that remarkable inhibitory effects on the accumulation of Aβ1-40 peptides were observed for SH-SY5Y cells treated with anionic HL-DMPS, though the accumulation was not inhibited by cationic HL-DMTAP. On the other hand, the immediate fusion of HL-DMTAP into SH-SY5Y cells was confirmed using a confocal laser microscope. Interestingly, the specific interactions between anionic HL-DMPS and Aβ1-40 peptides were observed using the thioflavin T (ThT) assay. In addition, the cytotoxicity of Aβ1-42 peptides on the SH-SY5Y cells decreased after the treatment with HL-DMPS. These results suggest that anionic HL-DMPS could be used as a novel medicine for AD in the future.