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首页> 外文期刊>The Journal of Nutritional Biochemistry >Folic acid administration inhibits amyloid beta-peptide accumulation in APP/PS1 transgenic mice
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Folic acid administration inhibits amyloid beta-peptide accumulation in APP/PS1 transgenic mice

机译：叶酸给药抑制APP / PS1转基因小鼠的淀粉样β肽积累

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摘要

Alzheimer's disease (AD) is associated with malnutrition, altered one-carbon metabolism and increased hippocampal amyloid-D peptide (AD) accumulation. Aberrant DNA methylation may be an epigenetic mechanism that underlies AD pathogenesis. We hypothesized that folic acid acts through an epigenetic gene silencing mechanism to lower AD levels in the APP/PSI transgenic mouse model of AD. APP/PSI mice were fed either folate-deficient or control diets and gavaged daily with 120 mu g/kg folic acid, 13.3 mg/kg S-adenosylmethionine (SAM) or both. Examination of the mice after 60 days of treatment showed that serum folate concentration increased with intake of folic acid but not SAM. Folate deficiency lowered endogenous SAM concentration, whereas neither intervention altered S-adenosylhomocysteine concentration. DNA methyltransferase (DNMT) activity increased with intake of folic acid raised DNMT activity in folate-deficient mice. DNA methylation rate was stimulated by folic acid in the amyloid precursor protein (APP) promoter and in the presenilin 1 (PSI) promoter. Folate deficiency elevated hippocampal APP, PSI and AD protein levels, and these rises were prevented by folic acid. In conclusion, these findings are consistent with a mechanism in which folic acid increases methylation potential and DNMT activity, modifies DNA methylation and ultimately decreases APP, PSI and AD protein levels. (C) 2015 Elsevier Inc. All rights reserved.
机译：阿尔茨海默氏病（AD）与营养不良，单碳代谢改变和海马淀粉样D肽（AD）积累增加有关。 DNA甲基化异常可能是AD发病机理的表观遗传机制。我们假设叶酸通过表观遗传基因沉默机制起作用，以降低AD的APP / PSI转基因小鼠模型中的AD水平。给APP / PSI小鼠饲喂叶酸缺乏或对照饮食，每天用120μg / kg的叶酸，13.3 mg / kg的S-腺苷甲硫氨酸（SAM）或两者同时灌胃。治疗60天后对小鼠进行的检查显示，血清叶酸浓度随叶酸的摄入而增加，但不随SAM的增加而增加。叶酸缺乏降低了内源性SAM的浓度，而两种干预均未改变S-腺苷同型半胱氨酸的浓度。叶酸缺乏小鼠DNA甲基转移酶（DNMT）活性随叶酸摄入量的增加而增加。淀粉样前体蛋白（APP）启动子和早老素1（PSI）启动子中的叶酸刺激DNA甲基化速率。叶酸缺乏会升高海马APP，PSI和AD蛋白水平，而叶酸可阻止这些升高。总之，这些发现与叶酸增加甲基化潜力和DNMT活性，修饰DNA甲基化并最终降低APP，PSI和AD蛋白水平的机制一致。 （C）2015 Elsevier Inc.保留所有权利。

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