Inhibiting microRNA-142–5p improves learning and memory in Alzheimer’s disease rats via targeted regulation of the PTPN1-mediated Akt pathway

Abstract

ObjectiveMicroRNAs (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. MethodsThe AD model was established by injection of Aβ1–42 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. ResultsOverexpressed 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. ConclusionDown-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.