多项研究表明，beta-淀粉样蛋白(Abeta)的毒性与氧化应激在阿尔茨海默症(AD)的发病机制中起着相互增强的作用。Abeta诱导神经细胞产生氧化应激，而氧化应激在介导Abeta细胞毒性的同时促进Abeta从淀粉样蛋白前体产生。体外研究显示，虾青素可以抑制Abeta诱导的细胞凋亡及活性氧的产生。然而，在动物模型中虾青素对Abeta神经毒性的作用及其机制仍不明确。本项目将利用神经细胞模型和AD转基因动物模型深入研究虾青素对Abeta神经毒性的抑制作用及其分子机理。重点探讨虾青素对AD转基因秀丽隐杆线虫和小鼠模型中Abeta诱导的氧化应激和病理行为的抑制作用；以及在神经细胞和AD小鼠模型中虾青素对细胞生存信号以及Abeta生成的影响。研究结果将使我们进一步了解虾青素对Abeta神经毒性的抑制作用及其分子机制，为明确虾青素的神经保护功能及其未来应用提供理论基础。

Multiple lines of evidence suggest that beta-amyloid (Abeta) neurotoxicity and oxidative stress are interlinked in the pathogenesis of Alzheimer's disease (AD). Abeta induction causes oxidative stress, while oxidative stress is shown to mediate Abeta cytotoxicity as well as to promote the Abeta generation from the amyloid precursor protein. Therefore, antioxidants may exert neuroprotective effects in AD through both direct inhibition of oxidative injury and reduction of Abeta production. Astaxanthin is a carotenoid with strong antioxidant properties. It has been reported in cell models that astaxanthin has inhibitory effects on Abeta-induced toxicity including apoptosis and the generation of reactive oxygen species. However, it is unknown whether astaxanthin has protective effects against Abeta-induced neurotoxicity in AD animal models. And the exact mechanisms by which astaxanthin protects against Abeta-induced neurotoxicity are unclear. In this project，we will study the effect of astaxanthin on Abeta-induced oxidative stress and pathological behaviors in transgenic AD Caenorhabditis elegans and mouse models. To explore the protective mechanisms of astaxanthin against Abeta-induced neurotoxicity, we will study the effects of astaxanthin on the survival signals in response to Abeta stimulation or oxidative stress, and the effects of astaxanthin on the production of Abeta in neuronal cells and AD mouse models. These proposed studies will further our understanding of the neuroprotective function of astaxanthin, providing insights for its future application.