miR-129 Promotes the Proliferation of Alzheimer's Neuronal Cells by Binding the 3 ' Untranslated Regions (3 ' UTR) of Amyloid Precursor Protein (APP)

Alzheimer's disease (AD) is a neurodegenerative disease with memory loss and cognitive impairment. Short non-coding RNAs (miRNAs) are potential biomarkers and therapeutic targets for AD. This study aims to investigate miR-129's role in AD. miR-129 and amyloid precursor protein (APP) expression was measured by Q-PCR, and LC3, p62, ATG5, Bcl-2, p-Tau and Caspase3 protein was detected by Western blot. Hydrogenase kits and DCFH-DA detected cell apoptosis, cytotoxicity and ROS generation. The interaction between APP and miR-129 was assessed by luciferase report experiment. HE staining and TUNEL assay evaluated hippocampal neuron damage. In AD patient serum, AD transgenic (TG) mouse brain tissue, and AB1-42-treated SH-SY5Y cells, miR-129 was downregulated but autophagy was increased. Overexpression of miR-129 reduced cell damage induced by AB1-42, and miR-129 can directly regulate APP expression by binding APP 3'-UTR. miR-129 inhibitors reversed the protective effect of shAPP on AB1-42-induced cell damage. In addition, miR-129 overexpression reduced neuronal damage through inhibiting autophagy in vivo. APP expression in AD patient and AD cell model was significantly increased compared to controls. A beta 1-42 treatment caused up-regulation of APP expression, while APP knockdown inhibited neurons through autophagy. In conclusion, miR-129 overexpression can regulate autophagy by targeting APPS, thereby reducing neuronal damage in AD. These findings provide a new perspective for treating AD.