Liang Weiwei, Xie Zhuojun, Liao Dong, Li Ying, Li Zhengyu, Zhao Yuanru, Li Xiaobo, Dong Manli
Department of General Practice, The First People's Hospital of Yunnan Province, Kunming, Yunnan, China.
Department of The Third outpatient, The First People's Hospital of Yunnan Province, Kunming, Yunnan, China.
Brain Res Bull. 2023 Jan;192:107-114. doi: 10.1016/j.brainresbull.2022.02.016. Epub 2022 Feb 24.
MicroRNAs (miRNAs) have been recognized as possible biomarkers for Alzheimer's disease (AD). MiR-142-5p has been reported to be abnormally expressed in brain tissues. However, the role of miR-142-5p in AD pathogenesis keeps unclear. This study aimed to investigate the effect of miR-142-5p on the learning and memory of AD rats via regulation of protein tyrosine phosphatase nonreceptor type 1 (PTPN1)-mediated protein kinase B (Akt) pathway.
The AD model was established by injection of Aβ oligomer once into the lateral ventricle of rats, and the spatial learning and memory ability of rats was measured. AD rats were injected with miR-142-5p or PTPN1 vectors to explore their functions in inflammation, Aβ, p-tau protein, apoptosis in brain tissues, and the effects on Akt pathway. The targeting relationship between miR-142-5p and PTPN1 was detected.
Overexpressed miR-142-5p, down-regulated PTPN1 and inactivated Akt pathway were exhibited in AD. MiR-142-5p targeted PTPN1 to mediate Akt pathway. Reduced miR-142-5p and elevated PTPN1 improved the behavior of AD rats. MiR-142-5p targeted PTPN1 to effectively inhibit Aβ formation and abnormal phosphorylation of p-tau protein, suppress the inflammation in the brain tissues of AD rat, and improve the survival rate of brain tissue cells. MiR-142-5p regulated PTPN1 to activate the Akt pathway, further inhibiting the apoptosis of brain neurons in AD rats.
Down-regulating miR-142-5p targets PTPN1 to activate Akt pathway, thus improving the learning and memory of AD rats and playing an anti-AD role.
微小RNA（miRNA）已被认为是阿尔茨海默病（AD）潜在的生物标志物。据报道，miR-142-5p在脑组织中表达异常。然而，miR-142-5p在AD发病机制中的作用仍不清楚。本研究旨在通过调节蛋白酪氨酸磷酸酶非受体1型（PTPN1）介导的蛋白激酶B（Akt）信号通路，探讨miR-142-5p对AD大鼠学习记忆的影响。
通过向大鼠侧脑室一次性注射Aβ寡聚体制备AD模型，并检测大鼠的空间学习记忆能力。给AD大鼠注射miR-142-5p或PTPN1载体，以探究它们在炎症、Aβ、p-tau蛋白、脑组织细胞凋亡中的作用以及对Akt信号通路的影响。检测miR-142-5p与PTPN1之间的靶向关系。
AD大鼠表现为miR-142-5p过表达、PTPN1下调和Akt信号通路失活。miR-142-5p靶向PTPN1以介导Akt信号通路。降低miR-142-5p水平并提高PTPN1表达可改善AD大鼠的行为。miR-142-5p靶向PTPN1可有效抑制Aβ形成和p-tau蛋白异常磷酸化，抑制AD大鼠脑组织炎症，并提高脑组织细胞存活率。miR-142-5p通过调节PTPN1激活Akt信号通路，进一步抑制AD大鼠脑神经元凋亡。
下调miR-142-5p靶向PTPN1激活Akt信号通路，从而改善AD大鼠的学习记忆能力，发挥抗AD作用。
