Department of Chemistry and Biochemistry, The University of Alabama, 1007E Shelby Hall, Tuscaloosa, AL 35487, USA.
Int J Mol Sci. 2023 Mar 8;24(6):5175. doi: 10.3390/ijms24065175.
The aggregation of amyloid beta (Aβ) into fibrillar aggregates is a key feature of Alzheimer's disease (AD) pathology. β-carotene and related compounds have been shown to associate with amyloid aggregates and have direct impact on the formation of amyloid fibrils. However, the precise effect of β-carotene on the structure of amyloid aggregates is not known, which poses a limitation towards developing it as a potential AD therapeutic. In this report, we use nanoscale AFM-IR spectroscopy to probe the structure of Aβ oligomers and fibrils at the single aggregate level and demonstrate that the main effect of β-carotene towards modulating Aβ aggregation is not to inhibit fibril formation but to alter the secondary structure of the fibrils and promote fibrils that lack the characteristic ordered beta structure.
淀粉样蛋白β（Aβ）聚集形成纤维状聚集体是阿尔茨海默病（AD）病理学的一个关键特征。β-胡萝卜素和相关化合物已被证明与淀粉样蛋白聚集体结合，并直接影响淀粉样纤维的形成。然而，β-胡萝卜素对淀粉样蛋白聚集体结构的确切影响尚不清楚，这限制了将其开发为潜在的 AD 治疗药物。在本报告中，我们使用纳米级原子力显微镜-红外光谱法（AFM-IR）在单个聚集体水平上探测 Aβ低聚物和纤维的结构，并证明β-胡萝卜素调节 Aβ聚集的主要作用不是抑制纤维形成，而是改变纤维的二级结构，并促进缺乏特征性有序β结构的纤维。
