The study of miR-423-5p upregulated in human Alzheimer's disease patients and 5XFAD mouse

Abstract

Alzheimer's Disease (AD) is the progressive neurodegenerative disorder and is the leading cause of dementia. Neurotoxicity induced by the accumulation of extracellular Amyloid-β (Aβ) plaques causes irreversible death of neuronal cells through mechanisms that is not fully understood. Here, I focused on the cellular function of microRNAs (miRNAs) regulating expression of genes involved in Aβ pathology. In microarray analysis of human plasma, pre-miR-423 showed the most significant increase in the groups of patients with mild cognitive impairment (MCI) or AD. In a 5xFAD mouse model, the expression of mature miR-423-5p was identical to that of pre-miR-423, indicating that the working strand of pre-miR-423 was miR-423-5p. The expression level of miR-423-5p increased from 4 months when Aβ plaque deposition began, and increased when primary cortical neurons from mouse or SH-SY5Y cells were treated with Aβ oligomers. Database analyses and reporter gene assays revealed that the increased miR-423-5p directly bound to the 3' untranslated region (3'UTR) of 1-phosphatidylinositol-4,5-bisphosphate phosphodiesterase beta-1 (PLCB1) and downregulated its expression. The Aβ oligomer-mediated increase in PLCB1 was restored to normal levels by further overexpression of miR-423-5p in SH-SY5Y cells. These findings suggest that miR-423-5p may be used as an early biomarker and a potential therapeutic strategy to protect cells against overloaded PLCB1 in the late stage of AD.