Department of Chemistry, Texas Christian University, 2800 S. University, Ft. Worth, Texas 76129, United States.
ACS Chem Neurosci. 2012 Nov 21;3(11):919-27. doi: 10.1021/cn300060v. Epub 2012 Aug 31.
Alzheimer's disease is a neurodegenerative disorder characterized by the development of intracellular neurofibrillary tangles, deposition of extracellular amyloid beta (Aβ) plaques, along with a disruption of transition metal ion homeostasis in conjunction with oxidative stress. Spectroscopic, transmission electron microscopy, and scanning electron microscopy imaging studies show that 1 (pyclen) is capable of both preventing and disrupting Cu(2+) induced AB(1-40) aggregation. The pyridine backbone of 1 engenders antioxidant capacity, as shown by cellular DCFH-DA (dichlorodihydrofluorescein diacetate) assay in comparison to other N-heterocyclic amines lacking this aromatic feature. Finally, 1 prevents cell death induced by oxidative stress as shown by the Calcein AM assay. The results are supported using density functional theory studies which show that the pyridine backbone is responsible for the antioxidant capacity observed.
阿尔茨海默病是一种神经退行性疾病,其特征是细胞内神经原纤维缠结的发展、细胞外淀粉样 β(Aβ)斑块的沉积,以及过渡金属离子稳态的破坏伴随着氧化应激。光谱、透射电子显微镜和扫描电子显微镜成像研究表明,1(piclén)能够预防和破坏 Cu(2+)诱导的 AB(1-40)聚集。1 的吡啶骨架产生抗氧化能力,这可以通过与缺乏这种芳香特征的其他 N-杂环胺的细胞 DCFH-DA(二氯二氢荧光素二乙酸酯)测定进行比较来证明。最后,1 通过 Calcein AM 测定防止氧化应激诱导的细胞死亡。结果得到密度泛函理论研究的支持,该研究表明吡啶骨架是观察到的抗氧化能力的原因。