dazolam inhibits the formation of amyloid fibrils and GM1 ganglioside-rich microdomains in presynaptic membranes through the gamma-aminobutyric acid A receptor.
dazolam inhibits the formation of amyloid fibrils and GM1 ganglioside-rich microdomains in presynaptic membranes through the gamma-aminobutyric acid A receptor.
复制标题
dazolam 通过 γ-氨基丁酸 A 受体抑制突触前膜中淀粉样原纤维和富含 GM1 神经节苷脂的微结构域的形成。
DOI：
10.1016/j.bbrc.2015.01.022
复制
发表时间：
2015
期刊：
影响因子：
--
通讯作者：
Sobue K
中科院分区：
文献类型：
--
作者：
Yamamoto N;Arima H;Sugiura T;Hirate H;Kusama N;Suzuki K;Sobue K
最近的研究表明，在全身麻醉下进行的手术干预与术后晚期发生阿尔茨海默病(AD)的风险呈正相关。有报道称，与AD密切相关的淀粉样蛋白-蛋白(Amyloidβ-Protein，Αβ)纤维形成在麻醉药的作用下加速。然而，这些效应背后的机制仍然不确定。本研究旨在研究麻醉剂咪达唑仑是否影响Αβ纤维形成，如果是，是否通过神经节苷脂作用于神经元表面。咪达唑仑治疗降低了神经元耐洗涤剂膜微区GM1的表达，这种作用受γ-氨基丁酸-A受体的调节。咪达唑仑可抑制神经元表面可溶性Αβ纤维的形成。此外，咪达唑仑在无细胞体系中抑制GM1诱导的纤维形成。此外，咪达唑仑抑制老年小鼠脑内分离的突触体中Αβ组装的形成。提示咪达唑仑对Αβ纤维形成有直接和间接的抑制作用。
Recent studies have suggested that a positive correlation exists between surgical interventions performed under general anesthesia and the risk of developing Alzheimer's disease (AD) in the late postoperative period. It has been reported that amyloid β-protein (Αβ) fibrillogenesis, which is closely related to AD, is accelerated by exposure to anesthetics. However, the mechanisms underlying these effects remain uncertain. This study was designed to investigate whether the anesthetic midazolam affects Αβ fibrillogenesis, and if so, whether it acts through GM1 ganglioside (GM1) on the neuronal surface. Midazolam treatment decreased GM1 expression in the detergent-resistant membrane microdomains of neurons, and these effects were regulated by the gamma-aminobutyric acid-A receptor. Midazolam inhibited Αβ fibril formation from soluble Αβ on the neuronal surface. In addition, midazolam suppressed GM1-induced fibril formation in a cell-free system. Moreover, midazolam inhibited the formation of Αβ assemblies in synaptosomes isolated from aged mouse brains. These finding suggested that midazolam has direct and indirect inhibitory effects on Αβ fibrillogenesis.