Neurospectroscopy and Neuroimaging Laboratory, National Brain Research Center, Manesar, Gurgaon, India.
J Alzheimers Dis. 2010;20(1):127-34. doi: 10.3233/JAD-2010-1350.
Amyloid-beta peptide (Abeta) oligomerization has a profound role in Alzheimer's disease pathophysiology. Biophysical studies have shown that smaller sized inhaled anesthetics promote oligomerization by inducing perturbation of three critical amino acid residues (G29, A30, and I31) located in the helix-loop-helix domain of Abeta. In this present experimental study, using state-of-the-art nuclear magnetic resonance, we have monitored the influence of a larger sized intravenous anesthetic, diazepam, as well as diazepam co-administered with halothane, on Abeta. It was concluded that diazepam (in isolation) does not interact with the G29, A30, and I31 residues, and no Abeta oligomerization occurs in the presence of 0.101 mM diazepam, even after 63 days. However, when diazepam was co-administered with halothane, profound Abeta oligomerization is observed. These results strengthen the hypothesis that the presence of smaller molecular sized anesthetic is instrumental in promoting Abeta oligomerization even when co-administered with a larger sized anesthetic, namely diazepam.
淀粉样蛋白-β肽 (Abeta) 寡聚化在阿尔茨海默病发病机制中起着重要作用。生物物理研究表明，较小的吸入性麻醉剂通过诱导 Abeta 螺旋环螺旋结构域中三个关键氨基酸残基 (G29、A30 和 I31) 的扰动促进寡聚化。在本实验研究中，我们使用最先进的核磁共振技术监测了较大的静脉麻醉剂地西泮以及地西泮与氟烷联合使用对 Abeta 的影响。结果表明，地西泮（单独使用）不会与 G29、A30 和 I31 残基相互作用，即使在 0.101mM 地西泮存在的情况下，Abeta 寡聚化也不会发生，即使经过 63 天也不会发生。然而，当地西泮与氟烷联合使用时，会观察到明显的 Abeta 寡聚化。这些结果加强了这样的假设，即即使与较大分子大小的麻醉剂（即地西泮）联合使用，较小分子大小的麻醉剂的存在对于促进 Abeta 寡聚化是至关重要的。
