Dataset Information

Down-regulation of EPB41L4A-AS1 mediated the brain aging and neurodegenerative diseases via damaging synthesis of NAD⁺ and ATP.

ABSTRACT:

Background

Aging and neurodegenerative diseases are typical metabolic-related processes. As a metabolism-related long non-coding RNA, EPB41L4A-AS has been reported to be potentially involved in the development of brain aging and neurodegenerative diseases. In this study, we sought to reveal the mechanisms of EPB41L4A-AS in aging and neurodegenerative diseases.

Methods

Human hippocampal gene expression profiles downloaded from the Genotype-Tissue Expression database were analyzed to obtain age-stratified differentially expressed genes; a weighted correlation network analysis algorithm was then used to construct a gene co-expression network of these differentially expressed genes to obtain gene clustering modules. Gene Ontology, Kyoto Encyclopedia of Genes and Genomes, protein-protein interaction network, and correlation analysis were used to reveal the role of EPB41L4A-AS1. The mechanism was verified using Gene Expression Omnibus dataset GSE5281 and biological experiments (construction of cell lines, Real-time quantitative PCR, Western blot, measurement of ATP and NAD⁺ levels, nicotinamide riboside treatment, Chromatin Immunoprecipitation) in neurons and glial-derived cells.

Results

EPB41L4A-AS1 was downregulated in aging and Alzheimer's disease. EPB41L4A-AS1 related genes were found to be enriched in the electron transport chain and NAD⁺ synthesis pathway. Furthermore, these genes were highly associated with neurodegenerative diseases and positively correlated with EPB41L4A-AS1. In addition, biological experiments proved that the downregulation of EPB41L4A-AS1 could reduce the expression of these genes via histone H3 lysine 27 acetylation, resulting in decreased NAD⁺ and ATP levels, while EPB41L4A-AS1 overexpression and nicotinamide riboside treatment could restore the NAD⁺ and ATP levels.

Conclusions

Downregulation of EPB41L4A-AS1 not only disturbs NAD⁺ biosynthesis but also affects ATP synthesis. As a result, the high demand for NAD⁺ and ATP in the brain cannot be met, promoting the development of brain aging and neurodegenerative diseases. However, overexpression of EPB41L4A-AS1 and nicotinamide riboside, a substrate of NAD⁺ synthesis, can reduce EPB41L4A-AS1 downregulation-mediated decrease of NAD⁺ and ATP synthesis. Our results provide new perspectives on the mechanisms underlying brain aging and neurodegenerative diseases.

SUBMITTER: Yang T

PROVIDER: S-EPMC8579638 | biostudies-literature | 2021 Nov

REPOSITORIES: biostudies-literature

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Publications

Down-regulation of EPB41L4A-AS1 mediated the brain aging and neurodegenerative diseases via damaging synthesis of NAD<sup>+</sup> and ATP.

Yang Tingpeng T Wang Yanzhi Y Liao Weijie W Zhang Shikuan S Wang Songmao S Xu Naihan N Xie Weidong W Luo Cheng C Wang Yangyang Y Wang Ziqiang Z Zhang Yaou Y

Cell & bioscience 20211110 1

<h4>Background</h4>Aging and neurodegenerative diseases are typical metabolic-related processes. As a metabolism-related long non-coding RNA, EPB41L4A-AS has been reported to be potentially involved in the development of brain aging and neurodegenerative diseases. In this study, we sought to reveal the mechanisms of EPB41L4A-AS in aging and neurodegenerative diseases.<h4>Methods</h4>Human hippocampal gene expression profiles downloaded from the Genotype-Tissue Expression database were analyzed t ...[more]

PMID: 34758883

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Dataset Information

Down-regulation of EPB41L4A-AS1 mediated the brain aging and neurodegenerative diseases via damaging synthesis of NAD⁺ and ATP.

Background

Methods

Results

Conclusions

Publications

Down-regulation of EPB41L4A-AS1 mediated the brain aging and neurodegenerative diseases via damaging synthesis of NAD<sup>+</sup> and ATP.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

Dataset Information

Down-regulation of EPB41L4A-AS1 mediated the brain aging and neurodegenerative diseases via damaging synthesis of NAD+ and ATP.

Background

Methods

Results

Conclusions

Publications

Down-regulation of EPB41L4A-AS1 mediated the brain aging and neurodegenerative diseases via damaging synthesis of NAD<sup>+</sup> and ATP.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

Down-regulation of EPB41L4A-AS1 mediated the brain aging and neurodegenerative diseases via damaging synthesis of NAD⁺ and ATP.