Du Y, Bales K R, Dodel R C, Liu X, Glinn M A, Horn J W, Little S P, Paul S M
Neuroscience Discovery Research, Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, Indiana 46285, USA.
J Neurochem. 1998 Mar;70(3):1182-8. doi: 10.1046/j.1471-4159.1998.70031182.x.
Beta-amyloid peptides (A beta) are deposited in an aggregated fibrillar form in both diffuse and senile plaques in the brains of patients with Alzheimer's disease. The neurotoxicity of A beta in cultured neurons is dependent on its aggregation state, but the factors contributing to aggregation and fibril formation are poorly understood. In the present study, we investigated whether alpha2-macroglobulin (alpha2M), a protein present in neuritic plaques and elevated in Alzheimer's disease brain, is a potential regulatory factor for A beta fibril formation. Previous studies in our laboratory have shown that alpha2M is an A beta binding protein. We now report that, in contrast to another plaque-associated protein, alpha1-antichymotrypsin, alpha2M coincubated with A beta significantly reduces aggregation and fibril formation in vitro. Additionally, cultured fetal rat cortical neurons are less vulnerable to the toxic actions of aged A beta following pretreatment with alpha2M. We postulate that alpha2M is able to maintain A beta in a soluble state, preventing fibril formation and associated neurotoxicity.
β-淀粉样肽（Aβ）以聚集的纤维状形式沉积在阿尔茨海默病患者大脑中的弥漫性斑块和老年斑中。Aβ在培养神经元中的神经毒性取决于其聚集状态，但导致聚集和纤维形成的因素尚不清楚。在本研究中，我们调查了α2-巨球蛋白（α2M），一种存在于神经炎性斑块中且在阿尔茨海默病大脑中升高的蛋白质，是否是Aβ纤维形成的潜在调节因子。我们实验室之前的研究表明，α2M是一种Aβ结合蛋白。我们现在报告，与另一种斑块相关蛋白α1-抗糜蛋白酶不同，与Aβ共同孵育的α2M在体外显著减少聚集和纤维形成。此外，用α2M预处理后，培养的胎鼠皮质神经元对老化Aβ的毒性作用的敏感性降低。我们推测，α2M能够使Aβ保持可溶状态，防止纤维形成和相关的神经毒性。
