Dokumacı Alim Hüseyin, Yerer Aycan Mukerrem Betul
Department of Pharmacology, Erciyes University Faculty of Pharmacy, Kayseri, Turkey.
Cytotechnology. 2019 Apr;71(2):635-646. doi: 10.1007/s10616-019-00312-7. Epub 2019 Apr 9.
The amyloid β (Aβ) toxic fibrils is thought to play a central role in the onset and progression of Alzheimer's disease (AD) because of it is a main formation of senile plaques. Diabetic patients are more vulnerable to caught Alzheimer's disease. Vildagliptine, a novel anti diabetic agent, has been reported to exert protective effects on AD rat models in restricted study. We aimed to investigate any protective effects of vildagliptine against Aβ fibrils on SH-SY5Y cell line. Vildagliptine decreased PSEN1 and PSEN2 mRNA levels which enroll Aβ production. In addition, vildagliptin was downregulated caspase-3 and caspase-9 expression levels which were evoked by Aβ. Also we confirmed cellular viability with real time cell analyzer and MTT assay. Our data exposed that vildagliptine has lowering effect on GSK3β and Tau phosphorylation. However we did not get protective effect of vildagliptine against Aβ toxicity on mitochondrial membrane potential. These results indicate that vildagliptine exerts a protective effect against Aβ by decreasing apoptosis related proteins, lowering GSK3β and Tau phosphorylation levels in addition to expression of PSEN1 and PSEN2 mRNA downregulation effect.
淀粉样β（Aβ）毒性纤维被认为在阿尔茨海默病（AD）的发病和进展中起核心作用，因为它是老年斑的主要组成形式。糖尿病患者更容易患阿尔茨海默病。维格列汀是一种新型抗糖尿病药物，在有限的研究中已报道其对AD大鼠模型具有保护作用。我们旨在研究维格列汀对SH-SY5Y细胞系中Aβ纤维的保护作用。维格列汀降低了参与Aβ产生的早老素1（PSEN1）和早老素2（PSEN2）的mRNA水平。此外，维格列汀下调了由Aβ诱导的半胱天冬酶-3（caspase-3）和半胱天冬酶-9（caspase-9）的表达水平。我们还通过实时细胞分析仪和MTT法确认了细胞活力。我们的数据表明，维格列汀对糖原合成酶激酶3β（GSK3β）和 Tau 磷酸化有降低作用。然而，我们未观察到维格列汀对Aβ毒性导致的线粒体膜电位具有保护作用。这些结果表明，维格列汀通过降低凋亡相关蛋白、降低GSK3β和 Tau 磷酸化水平以及下调PSEN1和PSEN2 mRNA的表达，对Aβ发挥保护作用。
