1. Academic Validation
  2. miR-146a aggravates cognitive impairment and Alzheimer disease-like pathology by triggering oxidative stress through MAPK signaling

miR-146a aggravates cognitive impairment and Alzheimer disease-like pathology by triggering oxidative stress through MAPK signaling

  • Neurologia (Engl Ed). 2021 Mar 11;S0213-4853(21)00022-0. doi: 10.1016/j.nrl.2020.12.006.
H Zhan-Qiang 1 Q Hai-Hua 2 Z Chi 3 W Miao 1 Z Cui 1 L Zi-Yin 1 H Jing 1 W Yi-Wei 4
Affiliations

Affiliations

  • 1 Department of General medicine, Affiliated Hospital of Chengde Medical College, Chengde 067000, China.
  • 2 Department of Dermatology, Affiliated Hospital of Chengde Medical College, Chengde 067000, China.
  • 3 Department of Neurology, Affilicated Hospital of Chengde Medical College, Chengde 067000, China.
  • 4 Department of General medicine, Affiliated Hospital of Chengde Medical College, Chengde 067000, China. Electronic address: wangyiwei9511_cmc@163.com.
Abstract

Introduction: Mir-146a-5p has been widely recognized as a critical regulatory element in the immune response. However, recent studies have shown that miR-146a-5p may also be involved in the development of Alzheimer disease (AD). Regrettably, the related mechanisms are poorly understood. Here, we investigated the effects of miR-146a in mice models and SH-SY5Y cells treated with amyloid β (Aβ)1-42.

Methods: To create a model of AD, SH-SY5Y cells were treated with Aβ1-42 and mice received intracerebroventricular injections of Aβ1-42. Then, the transcriptional levels of miR-146a were estimated by Real-Time PCR. We transiently transfected the miR-146a-5p mimic/inhibitor into cells and mice to study the role of miR-146a. The role of signaling pathways including p38 and Reactive Oxygen Species (ROS) was studied by using specific inhibitors. Aβ and amyloid-beta precursor protein (APP)levels were measured by immunoblotting. Furthermore, Aβ expression was analyzed by immunofluorescence and histochemical examinations.

Results: 1-42-stimulated SH-SY5Y cells displayed increased transcriptional levels of miR-146a and APP. Moreover, the p38 MAPK signaling pathway and ROS production were activated upon stimulation with a miR-146a-5p mimic. However, treatment with a miR-146a-5p inhibitor decreased the levels of APP, ROS, and p-p38 MAPK. A similar phenomenon was also observed in the Animals treated with Aβ1-42, in which miR-146a upregulation increased the expression of Aβ, p-p38, and ROS, while the inhibition of miR-146a had the opposite effect. This suggests that miR-146a increases Aβ deposition and ROS accumulation via the p-p38 signaling pathway.

Conclusions: Our research demonstrates that miR-146a-5pa increases Aβ deposition by triggering oxidative stress through activation of MAPK signaling.

Keywords

Alzheimer disease; Amyloid-β; Enfermedad de Alzheimer; Especies reactivas de oxígeno; MAPK signaling; Reactive oxygen species; Señalización MAPK; miR-146a-5p; β-amiloide.

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