2. Academic Validation
  3. NEAT1 regulates microtubule stabilization via FZD3/GSK3β/P-tau pathway in SH-SY5Y cells and APP/PS1 mice

NEAT1 regulates microtubule stabilization via FZD3/GSK3β/P-tau pathway in SH-SY5Y cells and APP/PS1 mice

  • Aging (Albany NY). 2020 Nov 18;12(22):23233-23250. doi: 10.18632/aging.104098.
Yiwan Zhao 1 2 3,  Ziqiang Wang 4,  Yunhao Mao 1 3 5,  Bing Li 1 2 3,  Yuanchang Zhu 1 2 3,  Shikuan Zhang 1 2 3,  Songmao Wang 2 3,  Yuyang Jiang 1,  Naihan Xu 1 3 5,  Yizhen Xie 6,  Weidong Xie 1 3 5,  Yaou Zhang 1 3 5
Affiliations

Affiliations

  • 1 State Key Laboratory of Chemical Oncogenomics, Tsinghua Shenzhen International Graduate School, Shenzhen 518055, P.R. China.
  • 2 School of Life Sciences, Tsinghua University, Beijing 100084, P.R. China.
  • 3 Key Lab in Healthy Science and Technology of Shenzhen, Tsinghua Shenzhen International Graduate School, Shenzhen 518055, P.R. China.
  • 4 Key Laboratory of Medical Reprogramming Technology, Shenzhen Second People’s Hospital, First Affiliated Hospital of Shenzhen University, Shenzhen 518035, P.R. China.
  • 5 Open FIESTA Center, Tsinghua University, Shenzhen 518055, P.R. China.
  • 6 State Key Laboratory of Applied Microbiology Southern China, Guangdong Provincial Key Laboratory of Microbial Culture Collection and Application, Guangdong Institute of Microbiology, Guangdong 510070, P.R. China.
PMID: 33221742 DOI: 10.18632/aging.104098
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.

Keywords

Alzheimer’s disease; FZD3; H3K27Ac; NEAT1; metformin.

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