NEAT1 involves Alzheimer’s Disease (AD) progression via regulation of glycolysis and P-tau
NEAT1 involves Alzheimer’s Disease (AD) progression via regulation of glycolysis and P-tau
Abstract Nuclear paraspeckles assembly transcript 1 (NEAT1) is a well-known long noncoding RNA (LncRNA) with unclear mechanism in Alzheimer’s disease (AD) progression. Here, we found that NEAT1 down-regulates in the early stage of AD patients and APPswe/PS1dE9 mouse. Moreover, knockdown of NEAT1 induced de-polymerization of microtubule (MT) and axonal retraction of nerve cells by dysregulation of the FZD3/GSK3β/p-tau signaling pathway. Histone acetylation analysis at the Frizzled Class Receptor 3 (FZD3) promoter shows a marked decreased in the levels of the H3K27 acetylation (H3K27Ac) after NEAT1 knockdown. Our data demonstrates that P300/CBP recruited by NEAT1 to the FZD3 promoter and induced its transcription via histone acetylation. In recent years a growing number of evidences have shown an abnormal brain glucose homeostasis in AD. In the present study we also observed an abnormal brain glucose homeostasis and enhanced sirtuin1 (SIRT1) activity after knockdown of NEAT similarly as in AD. Our results provided insight into the role of NEAT1 in the maintenance of MT stability and its effect on glucose metabolism during early stages of AD.
Wang Ziqiang、Li Bing、Wang Songmao、Zhu Yuanchang、Xie Yizhen、Xie Weidong、Zhao Yiwan、Xu Naihan、Mao Yunhao、Jiang Yuyang、Zhang Shikuan、Zhang Yaou
Key Laboratory of Medical Reprogramming Technology, Shenzhen Second People?ˉs Hospital, First Affiliated Hospital of Shenzhen UniversitySchool of Life Sciences, Tsinghua University||Key Lab in Healthy Science and Technology, Division of Life Science, Graduate School at Shenzhen, Tsinghua University||State Key Laboratory of Chemical Oncogenomics, Graduate School at Shenzhen, Tsinghua UniversityKey Lab in Healthy Science and Technology, Division of Life Science, Graduate School at Shenzhen, Tsinghua University||State Key Laboratory of Chemical Oncogenomics, Graduate School at Shenzhen, Tsinghua UniversitySchool of Life Sciences, Tsinghua University||Key Lab in Healthy Science and Technology, Division of Life Science, Graduate School at Shenzhen, Tsinghua University||State Key Laboratory of Chemical Oncogenomics, Graduate School at Shenzhen, Tsinghua UniversityState Key Laboratory of Applied Microbiology Southern China, Guangdong Provincial Key Laboratory of microbial Culture Collection and Application, Guangdong Institute of microbiologyKey Lab in Healthy Science and Technology, Division of Life Science, Graduate School at Shenzhen, Tsinghua University||State Key Laboratory of Chemical Oncogenomics, Graduate School at Shenzhen, Tsinghua University||Open FIESTA Center, Tsinghua UniversitySchool of Life Sciences, Tsinghua University||Key Lab in Healthy Science and Technology, Division of Life Science, Graduate School at Shenzhen, Tsinghua University||State Key Laboratory of Chemical Oncogenomics, Graduate School at Shenzhen, Tsinghua UniversityKey Lab in Healthy Science and Technology, Division of Life Science, Graduate School at Shenzhen, Tsinghua University||State Key Laboratory of Chemical Oncogenomics, Graduate School at Shenzhen, Tsinghua University||Open FIESTA Center, Tsinghua UniversitySchool of Life Sciences, Tsinghua University||State Key Laboratory of Chemical Oncogenomics, Graduate School at Shenzhen, Tsinghua University||Open FIESTA Center, Tsinghua UniversityKey Lab in Healthy Science and Technology, Division of Life Science, Graduate School at Shenzhen, Tsinghua UniversitySchool of Life Sciences, Tsinghua University||Key Lab in Healthy Science and Technology, Division of Life Science, Graduate School at Shenzhen, Tsinghua University||State Key Laboratory of Chemical Oncogenomics, Graduate School at Shenzhen, Tsinghua UniversityKey Lab in Healthy Science and Technology, Division of Life Science, Graduate School at Shenzhen, Tsinghua University||State Key Laboratory of Chemical Oncogenomics, Graduate School at Shenzhen, Tsinghua University||Open FIESTA Center, Tsinghua University
神经病学、精神病学基础医学分子生物学
Alzheimer’s DiseaseNEAT1FZD3H3K27AcGlycolysis
Wang Ziqiang,Li Bing,Wang Songmao,Zhu Yuanchang,Xie Yizhen,Xie Weidong,Zhao Yiwan,Xu Naihan,Mao Yunhao,Jiang Yuyang,Zhang Shikuan,Zhang Yaou.NEAT1 involves Alzheimer’s Disease (AD) progression via regulation of glycolysis and P-tau[EB/OL].(2025-03-28)[2025-08-18].https://www.biorxiv.org/content/10.1101/643718.点此复制
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