NEAT1 regulates microtubule stabilization via FZD3/GSK3β/P-tau pathway in SH-SY5Y cells and APP/PS1 mice.
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.
['Zhao|Yiwan|Y|', 'Wang|Ziqiang|Z|', 'Mao|Yunhao|Y|', 'Li|Bing|B|', 'Zhu|Yuanchang|Y|', 'Zhang|Shikuan|S|', 'Wang|Songmao|S|', 'Jiang|Yuyang|Y|', 'Xu|Naihan|N|', 'Xie|Yizhen|Y|', 'Xie|Weidong|W|', 'Zhang|Yaou|Y|']
D000544:Alzheimer Disease D016564:Amyloid beta-Protein Precursor D000818:Animals D045744:Cell Line, Tumor D004195:Disease Models, Animal D051157:Frizzled Receptors D000071679:Glycogen Synthase Kinase 3 beta D006624:Hippocampus D006801:Humans D008687:Metformin D008810:Mice, Inbred C57BL D008822:Mice, Transgenic D008870:Microtubules D009474:Neurons D018696:Neuroprotective Agents D010766:Phosphorylation D053764:Presenilin-1 D062085:RNA, Long Noncoding D015398:Signal Transduction D016875:tau Proteins
NEAT1 FZD3 H3K27Ac metformin Alzheimer’s disease