阿尔茨海默病中一碳代谢调节miR-29a-DNA甲基化串扰

IF 11.1 1区 医学 Q1 CLINICAL NEUROLOGY
Tiziana Raia, Rosaria A. Cavallaro, Luiza Diniz Ferreira Borges, Stefano Cinti, Mariano Bizzarri, Isidre Ferrer, Marco Lucarelli, Andrea Fuso
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引用次数: 0

摘要

阿尔茨海默病(AD)的多因素特性强调了表观遗传学在影响不同病理通路中的作用。我们证明了单碳代谢在表观遗传学上影响ad样表型。在这里,我们研究了AD中甲基化和microrna之间的串扰。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

One-carbon metabolism modulates miR-29a–DNA methylation crosstalk in Alzheimer's disease

One-carbon metabolism modulates miR-29a–DNA methylation crosstalk in Alzheimer's disease

One-carbon metabolism modulates miR-29a–DNA methylation crosstalk in Alzheimer's disease

One-carbon metabolism modulates miR-29a–DNA methylation crosstalk in Alzheimer's disease

INTRODUCTION

Alzheimer's disease (AD)’s multifactorial nature stresses the role of epigenetics in affecting different pathological pathways. We demonstrated that one-carbon metabolism epigenetically impacts AD-like phenotype. Here, we investigated the crosstalk between methylation and microRNAs in AD.

METHODS

We altered one-carbon metabolism to induce hypo- and hyper-methylation, in SK-N-BE neuroblastoma cells and TgCRND8 mice. miRNAs were profiled through a polymerase chain reaction array, then we focused on miR-29a expression and methylation of its genomic locus. Finally, we assessed miR-29a expression and methylation in the brain of AD subjects.

RESULTS

MiR-29a was repressed in hypomethylating and expressed in hypermethylating conditions. The expression of miR-29a and of its target, BACE1, was inversely correlated.

DISCUSSION

We demonstrated for the first time that miR-29a is modulated by one-carbon metabolism through DNA methylation, disclosing the molecular mechanisms regulating BACE1 expression in AD. These data confirm miR-29a’s protective role in AD and support miR-29a as a potential biomarker for AD.

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来源期刊
Alzheimer's & Dementia
Alzheimer's & Dementia 医学-临床神经学
CiteScore
14.50
自引率
5.00%
发文量
299
审稿时长
3 months
期刊介绍: Alzheimer's & Dementia is a peer-reviewed journal that aims to bridge knowledge gaps in dementia research by covering the entire spectrum, from basic science to clinical trials to social and behavioral investigations. It provides a platform for rapid communication of new findings and ideas, optimal translation of research into practical applications, increasing knowledge across diverse disciplines for early detection, diagnosis, and intervention, and identifying promising new research directions. In July 2008, Alzheimer's & Dementia was accepted for indexing by MEDLINE, recognizing its scientific merit and contribution to Alzheimer's research.
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