MicroRNA-340-5p increases telomere length by targeting telomere protein POT1 to improve Alzheimer's disease in mice.

Alzheimer's disease (AD) is a chronic neurodegenerative disorder which is the primary cause of dementia in the elderly. Telomere attrition has been proposed as a hallmark of aging. Our study aimed to explore the mechanism of the protection of telomere 1 (POT1) in regulating telomere length and affecting cellular senescence in AD. The AD mouse model was established by d-galactose and aluminum chloride, and the water maze test and dark avoidance test were used to detect the behaviors of mice and confirm the success of AD mouse model. AD cell model was established with HT22 cells induced by Aß42 oligomers. POT1 expression in the AD model was detected by quantitative real-time polymerase chain reaction. Cellular telomere length in hippocampal tissue was analyzed by telomere restriction fragment. Localization of intracellular POT1, telomerase, and telomeres was analyzed by immunofluorescence and fluorescence in situ hybridization. Dual-luciferase assay was used to validate the targeted binding relationship between microRNA-340-5p (miR-340-5p) and POT1. After inhibiting POT1 expression, the symptoms of AD in mice were improved. Aß1-42 deposition was reduced, whereas telomere length and telomerase activity was increased. Dual-luciferase assay verified the binding relationship between miR-340-5p and POT1. An increase in miR-340-5p expression could alleviate cellular senescence and AD symptoms. miR-340-5p increased cellular telomere length and delayed cell senescence by inhibiting POT1 expression to improve AD symptoms. This study made a conclusion that miR-340-5p increased cellular telomere length and delayed cell senescence by inhibiting POT1 expression to improve AD symptoms in mice.

Expression of telomere repeat binding factor 1 and TRF2 in Alzheimer's disease and correlation with clinical parameters.

OBJECTIVE: The objective of this study was to investigate the expression of serum telomere repeat binding factor 1 (TRF1) and TRF2 in patients with Alzheimer's disease (AD) and their correlation with clinicopathological features. METHODS: Fifty AD subjects and 50 healthy controls were enrolled in this study. Enzyme-linked immunosorbent assay (ELISA) was used to determine the expression of TRF1 and TRF2 in the peripheral blood plasma. Correlation analysis was used to evaluate the correlation between the protein expression and AD clinical parameters. RESULTS: The expression of TRF1 in peripheral blood serum of AD patients was significantly higher than that of the control group (t = 5.533, P < 0.01) and TRF2 was lower than the control group (t = 2.627, P = 0.010). The expression of TRF1 was positively correlated with the history of coronary heart disease (Spearman's r = 0.298，P = 0.035). The expression of TRF1 and TRF2 was positively correlated with age (Pearson's r1 = 0.830，P1 < 0.01；Pearson's r2 = 0.942，P2 < 0.01), BMI (Pearson's r1 = 0.791，P1 < 0.01；Pearson's r2 = 0.941，P2 < 0.01), Aß42 (Pearson's r1 = 0.765，P1 < 0.01；Pearson's r2 = 0.926，P2 < 0.01) and Tau protein (Pearson's r1 = 0.648，P1 < 0.01；Pearson's r2 = 0.691，P2 < 0.01) in blood serum of AD patients. However, there was no significant difference between both proteins expression and the history of hypertension, diabetes or stroke. CONCLUSION: TRF1 and TRF2 may be both specific to peripheral blood serum of AD, and may be related to the development of AD.