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.
Objective: The objective of this study is to investigate the effects of a cationic gallium containing Pc
(GaCl-Pc) on Aβ fibril formation process.
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.
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.