Wang Steven S-S, Becerra-Arteaga Alejandro, Good Theresa A
Department of Chemical Engineering, Texas A&M University, TAMU 3122, College Station, Texas 77843-3122, USA.
Biotechnol Bioeng. 2002 Oct 5;80(1):50-9. doi: 10.1002/bit.10347.
beta-Amyloid peptide (Abeta) is the primary protein component of senile plaques in Alzheimer's disease and is believed to be responsible for the neurodegeneration associated with the disease. Abeta is toxic only when aggregated, however, the size and structure of the aggregated species associated with toxicity is unknown. In the present study, we developed a diffusion-based method to simultaneously separate and detect the biological activity of toxic Abeta oligomers and used the method to examine the relationship between size of aggregated protein and toxicity to SH-SY5Y cells. From these measurements, the effective diffusivity and hydrodynamic radius of the toxic oligomeric species of Abeta could be determined. A sensitivity analysis was performed to examine the effects of model assumptions used in data analysis on the effective diffusivity calculated. The method provides a new estimate of the size of small toxic Abeta species associated with fibril formation. This work contributes to our understanding of the relationship between Abeta structure and toxicity and with further refinements may aid in our ability to design agents which alter the Abeta aggregation/dissociation processes associated with neurotoxicity.
β-淀粉样肽（Aβ）是阿尔茨海默病中淀粉样斑块的主要蛋白质成分，被认为与该疾病相关的神经退行性变有关。然而，Aβ只有在聚集时才具有毒性，而与毒性相关的聚集物的大小和结构尚不清楚。在本研究中，我们开发了一种基于扩散的方法，用于同时分离和检测有毒Aβ寡聚体的生物活性，并使用该方法研究聚集蛋白大小与对SH-SY5Y细胞毒性之间的关系。通过这些测量，可以确定Aβ有毒寡聚体的有效扩散系数和流体动力学半径。进行了敏感性分析，以检查数据分析中使用的模型假设对计算出的有效扩散系数的影响。该方法为与原纤维形成相关的小毒性Aβ物种的大小提供了新的估计。这项工作有助于我们理解Aβ结构与毒性之间的关系，进一步完善后可能有助于我们设计改变与神经毒性相关的Aβ聚集/解离过程的药物。
