Alpha v integrins mediate beta-amyloid induced inhibition of long-term potentiation.
Alpha v integrins mediate beta-amyloid induced inhibition of long-term potentiation.
复制标题
αv整合素介导β-淀粉样蛋白诱导的长时程增强抑制。
作者：
β-淀粉样蛋白（Abeta）是阿尔茨海默病患者细胞外斑块的主要成分。最近的几项研究表明，急性应用 Abeta 会抑制海马中 LTP 的诱导。在目前的研究中，我们研究了整合素在体外齿状回和体内 CA1 中 Abeta 介导的 LTP 阻断中的作用。研究发现，在体外齿状回和体内 CA1 中，针对 α v 整合素亚基的选择性抗体可以阻止 Abeta 对 LTP 的抑制。相反，两种对照抗体没有阻止Abeta的这种作用。此外，含有αv的整联蛋白的小分子非肽拮抗剂和整联蛋白的另外两种拮抗配体，超纤连蛋白和解联蛋白echistatin，也阻止了LTP的Abeta抑制。这些研究表明，αv 整合素可能是阿尔茨海默病神经变性之前突触功能障碍的重要介质。
Beta-amyloid (Abeta) is the principal component of the extracellular plaques present in patients with Alzheimer's disease. Several studies have recently shown that acutely applied Abeta inhibits the induction of LTP in the hippocampus. In the present studies, we have investigated the role of integrins in such Abeta-mediated block of LTP in the dentate gyrus in vitro and in the CA1 in vivo. Selective antibodies to the alpha v integrin subunit were found to prevent the Abeta inhibition of LTP, both in the dentate gyrus in vitro and in the CA1 in vivo. In contrast, two control antibodies did not prevent such action of Abeta. In addition, a small molecule nonpeptide antagonist of alpha v-containing integrins and two other antagonistic ligands of integrins, superfibronectin and the disintegrin echistatin, also prevented the Abeta inhibition of LTP. These studies indicate that alpha v integrins may be important mediators of synaptic dysfunction prior to neurodegeneration in Alzheimer's disease.