Department of Neurology, The Second Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China.
Department of Neurology, Xinyang Central Hospital, Xinyang, Henan, China.
Cell Biol Int. 2021 Jun;45(6):1306-1315. doi: 10.1002/cbin.11576. Epub 2021 Mar 19.
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 Aβ 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. Aβ 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.
阿尔茨海默病（AD）是一种慢性神经退行性疾病，是老年人痴呆的主要原因。端粒磨损已被提出作为衰老的标志。我们的研究旨在探讨端粒 1（POT1）保护端粒长度和影响 AD 细胞衰老的机制。通过半乳糖和氯化铝建立 AD 小鼠模型，通过水迷宫试验和暗回避试验检测小鼠行为，确认 AD 小鼠模型的成功。通过 Aβ寡聚体诱导 HT22 细胞建立 AD 细胞模型。通过定量实时聚合酶链反应检测 AD 模型中的 POT1 表达。通过端粒限制片段分析海马组织中的细胞端粒长度。通过免疫荧光和荧光原位杂交分析细胞内 POT1、端粒酶和端粒的定位。双荧光素酶测定用于验证 microRNA-340-5p（miR-340-5p）与 POT1 之间的靶向结合关系。抑制 POT1 表达后，改善了 AD 小鼠的症状。减少 Aβ 沉积，而增加端粒长度和端粒酶活性。双荧光素酶测定验证了 miR-340-5p 与 POT1 之间的结合关系。miR-340-5p 表达增加可减轻细胞衰老和 AD 症状。miR-340-5p 通过抑制 POT1 表达增加细胞端粒长度并延缓细胞衰老，从而改善 AD 症状。本研究得出结论，miR-340-5p 通过抑制 POT1 表达增加细胞端粒长度并延缓细胞衰老，从而改善 AD 小鼠的症状。
