Downregulation of miR-33 Has Protective Effect Against Aβ₂₅₋₃₅-Induced Injury in SH-SH-SY5Y Cells
2020
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 Ass-induced neurotoxicity is proposed as a possible modality for treatment of AD. miR-33 has been proven to promote Ass secretion and impair Ass 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 Ass(2)(5)(-)(3)(5). 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 Ass(2)(5)(-)(3)(5)-induced inflammation, oxidative stress, apoptosis, and synaptic damage by suppressing activation of the Akt/mTOR pathway.
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