miR-584-5p suppresses Aβ1-42-induced apoptosis in Alzheimer's disease cell model via targeting of HDAC1.

BACKGROUND: Alzheimer's disease (AD) represents a profoundly detrimental neurodegenerative disorder, and early diagnosis coupled with effective treatment remains a major clinical challenge. MicroRNAs (miRNAs) have emerged as key regulators associated with pathological processes in AD. AIM: This study aimed to explore the expression pattern and the likely diagnostic value of miR-584-5p in AD, as well as its molecular mechanism of action in regulating β-amyloid (Aβ)-induced apoptosis. METHODS: Peripheral blood samples from 90 AD patients and age- and sex-matched controls were examined using RT-qPCR. Correlation analyses of miR-584-5p expression with key AD biomarkers (Aβ42, tTau, pTau) were performed in AD patients. Following exposure to 5 µM Aβ1-42, SH-SY5Y cells were employed in subsequent functional experiments. Bioinformatics analysis, a dual-luciferase reporter assay, and negative correlation analysis of plasma samples were conducted to verify the target gene of miR-584-5p. RESULTS: miR-584-5p was significantly downregulated in AD patients, and its expression correlated with Aβ42 (r = 0.665), total tau (tTau, r = -0.642), phosphorylated tau (pTau, r = -0.576), and Mini-Mental State Examination (MMSE) scores (r = 0.618), yielding an AUC of 0.864 in this single-center cohort. miR-584-5p overexpression inhibited 5 µM Aβ1-42-induced apoptosis in SH-SY5Y cells, an effect that was reversed by concurrent HDAC1 overexpression. Mechanistically, by targeting HDAC1, miR-584-5p modulates p53 acetylation and the Bcl-2/Bax pathway at the protein level. CONCLUSIONS: miR-584-5p exerted neuroprotective effects via the miR-584-5p/HDAC1 axis, offering new insights into AD pathogenesis and suggesting this axis as a candidate for further preclinical investigation.