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.

背景：淀粉样蛋白 β (Aβ) 肽沉积被认为是阿尔茨海默病 (AD) 的主要原因。以前，我们已经表明，含有中性酞菁 (Zn-Pc) 的 Zn 会抑制 Aβ 原纤维的形成。

目的：本研究的目的是研究含有 Pc 的阳离子镓 (GaCl-Pc) 对 Aβ 原纤维形成过程的影响。

方法和结果：通过在原纤维形成缓冲液中孵育合成的 Aβ 肽来诱导 Aβ 原纤维的形成，并通过 ThT 荧光测定评估原纤维的数量。GaCl-Pc 剂量依赖性地抑制 Aβ1-40 和 Aβ1-42 原纤维形成。它主要抑制 Aβ1-42 原纤维形成动力学的伸长期，而不是滞后期。蛋白质印迹结果表明它没有抑制其寡聚化过程，而是增加了它。此外，GaCl-Pc 在体外条件下剂量依赖性地破坏预先形成的 Aβ1-42 原纤维，并降低 APP 转基因 AD 模型小鼠（J20 品系）脑切片培养物中的 Aβ 水平。近红外扫描结果表明，GaCl-Pc 具有与 Aβ1-42 结合的能力。MTT 测定表明 GaCl-Pc 对培养的神经元细胞系 (A1) 没有毒性，相反，对 Aβ 诱导的毒性显示出保护作用。此外，它剂量依赖性地降低了 A1 培养物中 Aβ 诱导的活性氧水平。

结论：因此，我们的结果表明 GaCl-Pc 减少了 Aβ 聚集并使预先形成的原纤维不稳定。由于阳离子分子显示出更好的穿过血脑屏障的能力，因此阳离子 GaCl-Pc 可能对 AD 的治疗很重要。