Howard P. Isermann Department of Chemical and Biological Engineering and the Center for Biotechnology & Interdisciplinary Studies, Rensselaer Polytechnic Institute , Troy, New York 12180-3590, United States.
ACS Chem Neurosci. 2017 Mar 15;8(3):432-434. doi: 10.1021/acschemneuro.7b00037. Epub 2017 Feb 10.
Although the amyloid (abeta peptide, Aβ) hypothesis is 25 years old, is the dominant model of Alzheimer's disease (AD) pathogenesis, and guides the development of potential treatments, it is still controversial. One possible reason is a lack of a mechanistic path from the cleavage products of the amyloid precursor protein (APP) such as soluble Aβ monomer and soluble molecular fragments to the deleterious effects on synaptic form and function. From a review of the recent literature and our own published work including aggregation kinetics and structural morphology, Aβ clearance, molecular simulations, long-term potentiation measurements with inhibition binding, and the binding of a commercial monoclonal antibody, aducanumab, we hypothesize that the N-terminal domains of neurotoxic Aβ oligomers are implicated in causing the disease.
虽然淀粉样蛋白（abeta 肽，Aβ）假说已有 25 年的历史，是阿尔茨海默病（AD）发病机制的主要模型，并指导潜在治疗方法的开发，但它仍然存在争议。一个可能的原因是缺乏从淀粉样前体蛋白（APP）的裂解产物（如可溶性 Aβ单体和可溶性分子片段）到对突触形态和功能产生有害影响的机制途径。从对最近文献的回顾和我们自己发表的工作，包括聚集动力学和结构形态、Aβ清除、分子模拟、具有抑制结合的长时程增强测量以及商业单克隆抗体 aducanumab 的结合，我们假设神经毒性 Aβ 寡聚物的 N 端结构域与疾病的发生有关。
