Shatera Tabassum, Abdullah Md. Sheikh, Shozo Yano, Takahisa Ikeue, Shingo Mitaki, Makoto Michikawa and Atsushi Nagai* Pages 589 - 600 ( 12 )
Background: Amyloid β (Aβ) peptide deposition is considered as the main cause of Alzheimer’s disease (AD). Previously, we have shown that a Zn containing neutral phthalocyanine (Zn-Pc) inhibits Aβ fibril formation. </P><P> Objective: The objective of this study is to investigate the effects of a cationic gallium containing Pc (GaCl-Pc) on Aβ fibril formation process. </P><P> Methods and Result: Aβ fibril formation was induced by incubating synthetic Aβ peptides in a fibril forming buffer, and the amount of fibril was evaluated by ThT fluorescence assay. GaCl-Pc dosedependently inhibited both Aβ1-40 and Aβ1-42 fibril formation. It mainly inhibited the elongation phase of Aβ1-42 fibril formation kinetics, but not the lag phase. Western blotting results showed that it did not inhibit its oligomerization process, rather increased it. Additionally, GaCl-Pc destabilized preformed Aβ1- 42 fibrils dose-dependently in vitro condition, and decreased Aβ levels in the brain slice culture of APP transgenic AD model mice (J20 strain). Near-infrared scanning results showed that GaCl-Pc had the ability to bind to Aβ1-42. MTT assay demonstrated that GaCl-Pc did not have toxicity towards a neuronal cell line (A1) in culture rather, showed protective effects on Aβ-induced toxicity. Moreover, it dosedependently decreased Aβ-induced reactive oxygen species levels in A1 culture. </P><P> Conclusion: Thus, our result demonstrated that GaCl-Pc decreased Aβ aggregation and destabilized the preformed fibrils. Since cationic molecules show a better ability to cross the blood-brain barrier, cationic GaCl-Pc could be important for the therapy of AD.</P>
Alzheimer's disease, amyloid β peptide, fibril formation, cationic phthalocyanine, neuronal culture, cytotoxicity.
Department of Laboratory Medicine, Faculty of Medicine, Shimane University, 89-1 Enya Cho, Izumo 693-8501, Department of Laboratory Medicine, Faculty of Medicine, Shimane University, 89-1 Enya Cho, Izumo 693-8501, Department of Laboratory Medicine, Faculty of Medicine, Shimane University, 89-1 Enya Cho, Izumo 693-8501, Department of Chemistry, Graduate School of Science and Engineering, Shimane University, 1060 Nishikawatsu, Matsue 690-8504, Department of Neurology, Faculty of Medicine, Shimane University, 89-1 Enya Cho, Izumo 693-8501, Department of Biochemistry, Graduate School of Medical Sciences, Nagoya City University, Kawasumi 1 Mizuho, Nagoya 467-8601, Department of Neurology, Faculty of Medicine, Shimane University, 89-1 Enya Cho, Izumo 693-8501