National Brain Research Centre, Manesar, Gurgaon, India.
J Alzheimers Dis. 2010;22 Suppl 3:27-34. doi: 10.3233/JAD-2010-101128.
Laboratory research on anesthetic-induced structural changes of amyloid beta (Aβ) peptide, from normal monomeric α-helix to the micro-aggregated form, has generated much interest in the scientific community as Aβ oligomerization is considered a key step in Alzheimer disease pathogenesis. A comprehensive review of the interactions of Aβ peptide with anesthetics of different molecular sizes is summarized as follows. Smaller sized anesthetics could access and perturb the cavity containing crucial amino acid residues G29, A30 and I31 of Aβ peptide leading to Aβ oligomerization. However, bulkier sized anesthetics are sterically hindered from accessing the cavity containing these crucial residues and do not initiate Aβ oligomerization. Notably, when a small sized anesthetic is co-administered with a larger sized one, the latter does not prevent access of the small sized anesthetic to the cavity. The results of these biophysical studies are supported by animal model studies which indicate that inhaled small molecular anesthetics induce enhanced Aβ plaque deposition in transgenic mice with AD pathology. In this review, a molecular pathway for the A$\beta $-anesthetic interaction at the atomic level is presented.
实验室研究表明，麻醉剂可诱导淀粉样蛋白β（Aβ）肽发生结构变化，使其从正常的单体α-螺旋结构转变为微聚集状态。这种变化引起了科学界的广泛关注，因为 Aβ 寡聚化被认为是阿尔茨海默病发病机制中的关键步骤。本文对不同分子大小的麻醉剂与 Aβ 肽相互作用进行了全面综述，总结如下：较小的麻醉剂能够进入并扰乱 Aβ 肽中含有关键氨基酸残基 G29、A30 和 I31 的腔，从而导致 Aβ 寡聚化。然而，较大的麻醉剂由于空间位阻而无法进入含有这些关键残基的腔，因此不会引发 Aβ 寡聚化。值得注意的是，当小尺寸麻醉剂与大尺寸麻醉剂共同给药时，后者并不能阻止小尺寸麻醉剂进入该腔。这些生物物理研究的结果得到了动物模型研究的支持，这些研究表明，吸入小分子麻醉剂会导致 AD 病理转基因小鼠中 Aβ 斑块沉积增加。在本文中，提出了一种在原子水平上 Aβ-麻醉剂相互作用的分子途径。
