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阿尔茨海默病发病机制:叶酸是否发挥作用?

Alzheimer's disease pathogenesis: Is there a role for folate?

机构信息

Institute of Health & Society, University of Newcastle upon Tyne, United Kingdom.

Human Nutrition Unit, Department of Oncology & Metabolism, University of Sheffield, United Kingdom.

出版信息

Mech Ageing Dev. 2018 Sep;174:86-94. doi: 10.1016/j.mad.2017.10.001. Epub 2017 Oct 13.

Abstract

Epigenetic modifications, including changes in DNA methylation, have been implicated in a wide range of diseases including neurological diseases such as Alzheimer's. The role of dietary folate in providing methyl groups required for maintenance and modulation of DNA methylation makes it a nutrient of interest in Alzheimer's. Late onset Alzheimer's disease is the most common form of dementia and at present its aetiology is largely undetermined. From epidemiological studies, the interactions between folate, B-vitamins and homocysteine as well as the long latency period has led to difficulties in interpretation of the data, thus current evidence exploring the role of dietary folate in Alzheimer's is contradictory and unresolved. Therefore, examining the effects at a molecular level and exploring potential epigenetic mechanisms could increase our understanding of the disease and aetiology. The aim of this review is to examine the role that folate could play in Alzheimer's disease neuropathology and will focus on the effects of folate on DNA methylation which link to disease pathology, initiation and progression.

摘要

表观遗传修饰,包括 DNA 甲基化的改变,与包括神经退行性疾病(如阿尔茨海默病)在内的多种疾病有关。膳食叶酸在提供维持和调节 DNA 甲基化所需的甲基方面的作用使其成为阿尔茨海默病关注的营养素。晚发性阿尔茨海默病是最常见的痴呆形式,目前其病因在很大程度上尚未确定。从流行病学研究来看,叶酸、B 族维生素和同型半胱氨酸之间的相互作用以及潜伏期长,导致对数据的解释存在困难,因此,目前探索膳食叶酸在阿尔茨海默病中作用的证据存在矛盾且尚未解决。因此,在分子水平上研究其作用并探索潜在的表观遗传机制可以增进我们对疾病和病因的了解。本篇综述的目的是探讨叶酸在阿尔茨海默病神经病理学中的作用,并将重点关注叶酸对与疾病病理、发病和进展相关的 DNA 甲基化的影响。

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