Department of Bioengineering, Faculty of Engineering, Integral University, Lucknow 226026, India.
Department of Pharmacy, Abdul Wali Khan University Mardan 23200, Pakistan.
Molecules. 2019 Sep 5;24(18):3233. doi: 10.3390/molecules24183233.
Alzheimer's disease (AD) is a widespread dynamic neurodegenerative malady. Its etiology is still not clear. One of the foremost pathological features is the extracellular deposits of Amyloid-beta (Aβ) peptides in senile plaques. The interaction of Aβ and the receptor for advanced glycation end products at the blood-brain barrier is also observed in AD, which not only causes the neurovascular anxiety and articulation of proinflammatory cytokines, but also directs reduction of cerebral bloodstream by upgrading the emission of endothelin-1 to induce vasoconstriction. In this process, RAGE is deemed responsible for the influx of Aβ into the brain through BBB. In the current study, we predicted the interaction potential of the natural compounds vincamine, ajmalicine and emetine with the Aβ peptide concerned in the treatment of AD against the standard control, curcumin, to validate the Aβ peptide-compounds results. Protein-protein interaction studies have also been carried out to see their potential to inhibit the binding process of Aβ and RAGE. Moreover, the current study verifies that ligands are more capable inhibitors of a selected target compared to positive control with reference to ΔG values. The inhibition of Aβ and its interaction with RAGE may be valuable in proposing the next round of lead compounds for effective Alzheimer's disease treatment.
阿尔茨海默病（AD）是一种广泛存在的动态神经退行性疾病。其病因尚不清楚。最重要的病理学特征之一是老年斑中细胞外淀粉样β（Aβ）肽的沉积。AD 中还观察到 Aβ与血脑屏障中晚期糖基化终产物受体的相互作用，这不仅导致神经血管紧张和促炎细胞因子的表达，还通过增加内皮素-1 的释放来引导脑血流量减少，从而引起血管收缩。在这个过程中，RAGE 被认为负责通过 BBB 将 Aβ 内流到大脑中。在本研究中，我们预测了天然化合物长春胺、育亨宾和依米丁与用于治疗 AD 的 Aβ 肽的相互作用潜力，以验证 Aβ 肽-化合物的结果。还进行了蛋白质-蛋白质相互作用研究，以观察它们抑制 Aβ与 RAGE 结合过程的潜力。此外，本研究还验证了与阳性对照相比，配体针对选定靶标是更有效的抑制剂，这可以参考ΔG 值。抑制 Aβ及其与 RAGE 的相互作用可能有助于提出下一轮有效的阿尔茨海默病治疗的先导化合物。
