MicroRNA‐25 aggravates Aβ1‐42‐induced hippocampal neuron injury in Alzheimer's disease by downregulating KLF2 via the Nrf2 signaling pathway in a mouse model

Abstract

Recently, numerous microRNAs (miRNAs) have been considered as key players in the regulation of neuronal processes. The purpose of the present study is to explore the effect of miR‐25 on hippocampal neuron injury in Alzheimer's disease (AD) induced by amyloid β (Aβ) peptide fragment 1 to 42 (Aβ1‐42) via Kruppel‐like factor 2 (KLF2) through the nuclear factor‐E2‐related factor 2 (Nrf2) signaling pathway. A mouse model of AD was established through Aβ1‐42 induction. The underlying regulatory mechanisms of miR‐25 were analyzed through treatment of miR‐25 mimics, miR‐25 inhibitors, or small interfering RNA (siRNA) against KLF2 in hippocampal tissues and cells isolated from AD mice. The targeting relationship between miR‐25 and KLF2 was predicted using a target prediction program and verified by luciferase activity determination. MTT assay was used to evaluate the proliferative ability and flow cytometry to detect cell cycle distribution and apoptosis. KLF2 was confirmed as a target gene of miR‐25. When the mice were induced by Aβ1‐42, proliferation was suppressed while apoptosis was promoted in hippocampal neurons as evidenced by lower levels of KLF2, Nrf2, haem oxygenase, glutathione S transferase α1, glutathione, thioredoxin, and B‐cell lymphoma‐2 along with higher bax level. However, such alternations could be reversed by treatment of miR‐25 inhibitors. These findings indicate that miR‐25 may inhibit hippocampal neuron proliferation while promoting apoptosis, thereby aggravating hippocampal neuron injury through downregulation of KLF2 via the Nrf2 signaling pathway.

The microRNA-17 ~ 92 Family as a Key Regulator of Neurogenesis and Potential Regenerative Therapeutics of Neurological Disorders

“…The decay of miR-17~92 family can be associated with the production of Aβ plaque and hyperphosporylation of Tau, although the exact mechanisms remain ambiguous [64,65]. However, Duan and Si reported an unexpected elevation of miR-25 expression levels in hippocampal tissues of AD mice [66]. The misexpression of miR-25 can inhibit proliferation and induce cell apoptosis in AD mouse primary hippocampal cell culture, suggesting miR-17~92 may possess much more complex functions in the pathogenesis of neurodegenerative diseases than previously thought.…”

Total Glycosides of Cistanche deserticola Promote Neurological Function Recovery by Inducing Neurovascular Regeneration via Nrf-2/Keap-1 Pathway in MCAO/R Rats

“…Previous research shows that TGs can improve the survival rate of hippocampal pyramidal cells and induce neurogenesis (Lian et al, 2017). Oxidative stress causes the loss of neurons during lots of diseases, such as Parkinson, stroke, and so on (Duan and Si, 2019;Singh et al, 2019). Nrf-2 transcribes lots of genes related to neuro-protection in their promoter region, mainly including SOD, MDA, CAT, and gglutamyl cysteine ligases, etc (Satoh et al, 2006).…”

Functional roles and networks of non-coding RNAs in the pathogenesis of neurodegenerative diseases

“…Moreover, miR-25 directly targets KLF2 and Nrf2, which are associated with hippocampal neuron proliferation. Aβ42 treatment upregulates miR-25 to promote cell death in mouse models [115]. Upregulation of Heme oxygenase 1 (HMOX1) has been linked to cognitive function and downregulation of miR183-5p in an AD mouse model.…”