1. NEAT1 regulates microtubule stabilization via FZD3/GSK3β/P-tau pathway in SH-SY5Y cells and APP/PS1 mice
- Author
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Bing Li, Shikuan Zhang, Yaou Zhang, Yuyang Jiang, Ziqiang Wang, Weidong Xie, Yiwan Zhao, Songmao Wang, Yuanchang Zhu, Yunhao Mao, Yizhen Xie, and Naihan Xu
- Subjects
Aging ,Frizzled ,NEAT1 ,Mice, Transgenic ,tau Proteins ,H3K27Ac ,Hippocampus ,Microtubules ,Amyloid beta-Protein Precursor ,Downregulation and upregulation ,Alzheimer Disease ,Transcription (biology) ,Cell Line, Tumor ,Presenilin-1 ,Animals ,Humans ,Gene silencing ,Epigenetics ,Phosphorylation ,Neurons ,Glycogen Synthase Kinase 3 beta ,biology ,Chemistry ,Cell Biology ,Frizzled Receptors ,Metformin ,Paraspeckles ,Cell biology ,Mice, Inbred C57BL ,Disease Models, Animal ,Neuroprotective Agents ,Histone ,Acetylation ,biology.protein ,RNA, Long Noncoding ,Alzheimer’s disease ,Research Paper ,FZD3 ,Signal Transduction - Abstract
Nuclear paraspeckles assembly transcript 1 (NEAT1) is a well-known long noncoding RNA (lncRNA) with various functions in different physiological and pathological processes. Notably, aberrant NEAT1 expression is implicated in the pathogenesis of various neurodegenerative diseases, including Alzheimer's disease (AD). However, the molecular mechanism of NEAT1 in AD remains poorly understood. In this study, we investigated that NEAT1 regulated microtubules (MTs) polymerization via FZD3/GSK3β/p-tau pathway. Downregulation of NEAT1 inhibited Frizzled Class Receptor 3 (FZD3) transcription activity by suppressing H3K27 acetylation (H3K27Ac) at the FZD3 promoter. Our data also demonstrated that P300, an important histone acetyltransferases (HAT), recruited by NEAT1 to bind to FZD3 promoter and mediated its transcription via regulating histone acetylation. In addition, according to immunofluorescence staining of MTs, metformin, a medicine for the treatment of diabetes mellitus, rescued the reduced length of neurites detected in NEAT1 silencing cells. We suspected that metformin may play a neuroprotective role in early AD by increasing NEAT1 expression and through FZD3/GSK3β/p-tau pathway. Collectively, NEAT1 regulates microtubule stabilization via FZD3/GSK3β/P-tau pathway and influences FZD3 transcription activity in the epigenetic way.
- Published
- 2020