奈米粒子 C60 在預防 Aβ 所誘發之 Neuro 2A 神經細胞細胞毒性之作用   全文下載

C60 Fullerene Nanoparticle Prevents β-Amyloid Peptide Induced Cytotoxicity in Neuro 2A Cells

氧化壓力是阿茲海默症之早期決定因子，和aβ誘發細胞死亡之中介神經死亡有關。C60富勒烯已知像「自由基海綿」可以吸附自由基，而且比其他抗氧化物質更有效。在這個研究中，我們觀察C60富勒烯之衍生物Peg-C60-3在neuro-2a細胞β-amyloid (aβ)25-35誘發毒性之抗拮作用。我們發現Peg-C60-3能降低aβ25-35-誘發之細胞毒性。以微陣列技術觀察分析aβ25-35處理有關之基因表現，發現包括eR stress，離子通道、細胞週期、及抗氧化等相關基因表現具有關聯性。本研究證實C60可以降低aβ25-35對細胞的毒殺作用，並能逆轉aβ25-35處理之基因表現，提供細胞保護之機制。本研究結果提供對aβ25-35可能產生基因表現路徑及C60保護之機制有新的理解，希望能做為以富勒烯治療aβ相關疾病之藥物一些好的建議。

Oxidative stress, which is an early determinant of Alzheimer’s disease (AD), is involved in mediating neuronal apoptosis in Aβ-induced cell death. C60 fullerenes are known to behave like a “radical sponge” as they can sponge up free radicals and act more effectively than other antioxidants. PEG-C60-3, a C60 fullerene derivative, was investigated against β-amyloid (Aβ)25-35-induced toxicity toward Neuro-2A cells in this study. PEG-C60-3 reduced Aβ25-35-induced cytotoxicity, which showed an increasing cell viability with C60 and Aβ25-35 co-treated cells. Moreover, the intracellular reactive oxygen species (ROS) accumulation caused by Aβ-treated Neuro-2A cells was reduced by PEG-C60-3 co-treatment. Microarray for the analysis of gene expressions was investigated. Endoplasmic retic-ulum (ER) stress responsive genes, ion-channel, cell-cycle and anti-oxidant related cell responses were found to be associated with C60 protective mechanism against Aβ25-35 treatment. The results offered new comprehension into the possible pathway of Aβ25-35 gene expression and C60 protective mechanism. With the understanding of the roles of Aβ and C60 in cells, we can hopefully provide insight on therapeutic design using C60 fullerene nanoparticles against Aβ-associated diseases.