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02 March 2020 : Laboratory Research  

Downregulation of miR-33 Has Protective Effect Against Aβ₂₅₋₃₅-Induced Injury in SH-SH-SY5Y Cells

Xiaoping Wang1ABCDEF, Xiaojia Li1ABCDEFG*, Bin Huang1ACDF, Lili Yang1ABEF, Kai Chen1BCD, Dongdong Zhao2AEF, Xiangdong Luo1ABCD, Yingji Wang3BCDEF

DOI: 10.12659/MSM.921026

Med Sci Monit 2020; 26:e921026

Abstract

BACKGROUND: Alzheimer disease (AD) is a significant health issue for the elderly, and there are at present no clinically effective anti-AD agents. Prevention of Aβ-induced neurotoxicity is proposed as a possible modality for treatment of AD. miR-33 has been proven to promote Aβ secretion and impair Aβ clearance in neural cells. The present study assessed whether miR-33 is involved in AD pathology.

MATERIAL AND METHODS: miR-33 level was detected by qRT-PCR. The Akt/mTOR pathway was analyzed by Western blot analysis. Neuron inflammation and oxidative stress were measured using commercial detection kits. Flow cytometry and Western blot assay were conducted to assess cell apoptosis, and Western blot assay was used to assess synaptic protein levels.

RESULTS: miR-33 expression level was markedly upregulated in SH-SY5Y cells treated with Aβ₂₅₋₃₅. miR-33 knockdown suppressed inflammation, oxidative stress, and cell apoptosis. In addition, miR-33 knockdown improved synaptic plasticity, and the protective effect of miR-33 knockdown was discovered through suppressing activation of the Akt/mTOR signaling pathway.

CONCLUSIONS: Taken together, these findings suggest that miR-33 knockdown protects against Aβ₂₅₋₃₅-induced inflammation, oxidative stress, apoptosis, and synaptic damage by suppressing activation of the Akt/mTOR pathway.

Keywords: Alzheimer Disease, Autophagy, Neurology, Amyloid beta-Peptides, Apoptosis, Cells, Cultured, Down-Regulation, Gene Knockdown Techniques, Inflammation, MicroRNAs, Oxidative Stress, Peptide Fragments, Proto-Oncogene Proteins c-akt, Signal Transduction, Synapses, TOR Serine-Threonine Kinases

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Medical Science Monitor eISSN: 1643-3750
Medical Science Monitor eISSN: 1643-3750