MicroRNA‐140‐5p inhibitor attenuates memory impairment induced by amyloid‐ß oligomer in vivo possibly through Pin1 regulation

Abstract

Aims The peptidyl‐prolyl cis/trans isomerase, Pin1, has a protective role in age‐related neurodegeneration by targeting different phosphorylation sites of tau and the key proteins required to produce Amyloid‐β, which are the well‐known molecular signatures of Alzheimer's disease (AD) neuropathology. The direct interaction of miR‐140‐5p with Pin1 mRNA and its inhibitory role in protein translation has been identified. The main purpose of this study was to investigate the role of miRNA‐140‐5p inhibition in promoting Pin1 expression and the therapeutic potential of the AntimiR‐140‐5p in the Aß oligomer (AßO)‐induced AD rat model. Methods Spatial learning and memory were assessed in the Morris water maze. RT‐PCR, western blot, and histological assays were performed on hippocampal samples at various time points after treatments. miRNA‐140‐5p inhibition enhanced Pin1 and ADAM10 mRNA expressions but has little effect on Pin1 protein level. Results The miRNA‐140‐5p inhibitor markedly ameliorated spatial learning and memory deficits induced by AßO, and concomitantly suppressed the mRNA expression of inflammatory mediators TNFα and IL‐1β, and phosphorylation of tau at three key sites (thr231, ser396, and ser404) as well as increased phosphorylated Ser473‐Akt. Conclusion According to our results, Antimir‐140‐mediated improvement of AβO‐induced neuronal injury and memory impairment in rats may provide an appropriate rationale for evaluating miR‐140‐5p inhibitors as a promising agent for the treatment of AD.

Circulating microRNA miR-425-5p Associated with Brain White Matter Lesions and Inflammatory Processes

“…Risk factor for memory impairment induced by Aβ [64] Associated with neurodegenerative diseases in general [65] Associated with vascular cognitive impairment [66] Associated with cognitive performance in healthy older adults [67] Associated with AD risk gene ADAM10 [68] Neuroprotective effects [69] In this paper, we provide the first study with a comprehensive association analysis between miRNA alterations and WMLs in a large general population sample. We propose hsa-miR-425-5p as a promising candidate probably involved in inflammatory mechanisms.…”

Function and regulation of cis P‐tau in the pathogenesis and treatment of conventional and nonconventional tauopathies

“…In addition, cobalt causes neurodegeneration via reducing Pin1 expression and consequently altering Pin1 substrates, including P-tau, APP, Aβ, and GSK3β (Zheng et al, 2021). MiR-140-5p inhibitor enhances Pin1 expression and ameliorates Aβ induced learning and memory deficits (Khodabakhsh et al, 2022).…”