Depletion of LncRNA NEAT1 Rescues Mitochondrial Dysfunction Through NEDD4L-Dependent PINK1 Degradation in Animal Models of Alzheimer's Disease

Frontiers in Cellular Neuroscience
Zhonghua HuangJie Zhang

Abstract

Alzheimer's disease (AD) is the most common neurodegenerative disorder and the main cause of dementia among the elderly worldwide. Unfortunately, the mechanism of AD remains unclear, and no effective therapies are available yet. An increasing amount of studies have demonstrated that long non-coding RNAs (LncRNAs) play a notable role in the pathogenesis of plenty of human diseases, and they have served as biomarkers and potential therapeutic targets. However, the function of LncRNAs in AD remains unclear. This study aimed to explore the potential role of LncRNA nuclear enriched abundant transcript 1 (NEAT1) in AD. We found that LncRNA NEAT1 was upregulated in the AD animal models. Furthermore, we demonstrated that NEAT1 could interact with NEDD4L and promote PTEN-induced putative kinase 1 (PINK1)'s ubiquitination and degradation and then impaired PINK1-dependent autophagy. Collectively, the lncRNA NEAT1 promotes the pathogenesis of AD and serves as a promising novel target for pharmacological intervention.

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Citations

Nov 17, 2020·Frontiers in Physiology·Léa Lescouzères, Pascale Bomont
Dec 17, 2020·Journal of Parkinson's Disease·Fanni Annamária BorosPéter Klivényi
Nov 13, 2020·Frontiers in Neurology·Xuewen XiaoBin Jiao
Mar 23, 2021·BioEssays : News and Reviews in Molecular, Cellular and Developmental Biology·Finn McCluggage, Archa H Fox
Apr 27, 2021·Non-coding RNA Research·Zhenxing SongChuan Huang
Oct 21, 2020·Seminars in Cell & Developmental Biology·Ryan A SzetoCleber A Trujillo
Jul 29, 2021·Journal of Cellular and Molecular Medicine·Xiaoyu Dong, Shuyan Cong
Aug 21, 2021·Journal of Molecular Neuroscience : MN·Soudeh Ghafouri-FardMohammad Samadian

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Methods Mentioned

BETA
transgenic
ELISA
Pull-Down
PCR
transfection
Immunoprecipitation
Assay
co-immunoprecipitation
co-immunoprecipitation assay
ubiquitination

Software Mentioned

GraphPad
Encyclopedia DNA Elements ( ENCODE

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