Ding Haojun
Henan Vocational College of Industry and Trade, Zhengzhou 450000, China.
Galen Med J. 2023 May 13;12:e3027. doi: 10.31661/gmj.v12i0.3027. eCollection 2023.
Alzheimer's disease (AD) is the most important neurogenerative disorder with progressive dementia as its main clinical manifestation. The microRNAs (miRNAs) are identified as crucial modulators in AD progression. Nevertheless, the biological potential of miR-21 in AD is obscure. Hence, this study aimed to evaluate the possible role of miR-21 in the pathogenesis of AD via phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K)/protein kinase B (AKT)/glycogen synthase kinase-3beta (GSK-3β) signaling.
The miR-21 expression in the brain tissues of patients with AD, as well as normal brain tissues and Aβ1-42-stimulated SH-SY5Y cell line (AD model) was examined by in situ hybridization and quantitative real-time polymerase chain reaction. Also, the apoptosis-linked protein levels as well as programmed cell death 4 (PDCD4) were detected by western blot.
Our findings revealed that miR-21 was low expressed in the brain tissues of patients with AD and AD model (P0.01). Also, the miR-21 overexpression could inhibit apoptosis of the AD model (P0.01). Indeed, the miR-21 negatively regulated PDCD4 expression, which led to activated PI3K/AKT/GSK-3β signaling.
Our study demonstrated that miR-21 cloud inhibits cell apoptosis in AD through the activation of PI3K/AKT/GSK-3β signaling pathway using inhibition of PDCD4 expression.
阿尔茨海默病（AD）是最重要的神经退行性疾病，以进行性痴呆为主要临床表现。微小RNA（miRNA）被认为是AD进展中的关键调节因子。然而，miR-21在AD中的生物学潜能尚不清楚。因此，本研究旨在通过磷脂酰肌醇-4,5-二磷酸3-激酶（PI3K）/蛋白激酶B（AKT）/糖原合酶激酶-3β（GSK-3β）信号通路评估miR-21在AD发病机制中的可能作用。
通过原位杂交和定量实时聚合酶链反应检测AD患者脑组织、正常脑组织以及Aβ1-42刺激的SH-SY5Y细胞系（AD模型）中miR-21的表达。此外，通过蛋白质印迹法检测凋亡相关蛋白水平以及程序性细胞死亡4（PDCD4）。
我们的研究结果显示，miR-21在AD患者脑组织和AD模型中低表达（P<0.01）。此外，miR-21过表达可抑制AD模型的细胞凋亡（P<0.01）。实际上，miR-21负向调节PDCD4表达，从而激活PI3K/AKT/GSK-3β信号通路。
我们的研究表明，miR-21可通过抑制PDCD4表达激活PI3K/AKT/GSK-3β信号通路，从而抑制AD中的细胞凋亡。
