Epigenetic changes in the progression of Alzheimer's disease.
Epigenetic changes in the progression of Alzheimer's disease.
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DOI：
10.1016/j.mad.2013.08.005
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发表时间：
2013-10
影响因子：
5.3
通讯作者：
Lovell, M. A.
中科院分区：
文献类型：
--
作者：
Bradley-Whitman, M. A.;Lovell, M. A.
DNA去甲基化的关键中间体5-羟甲基胞嘧啶（5 hmC）的形成由将5-甲基胞嘧啶（5 mC）氧化为5 hmC的蛋白质的10 - 11易位（泰特）家族驱动。为了确定甲基化/去甲基化状态是否在阿尔茨海默病（AD）的进展过程中改变，在来自5名年龄匹配的正常对照的海马/海马旁回（HPG）和小脑的核DNA中定量TET 1、5 mC和随后的中间体（包括5 hmC、5-甲酰胞嘧啶（5 fC）和5-羧基胞嘧啶（5caC））的水平，5例临床前AD（PCAD）受试者和7例晚期AD（LAD）受试者（通过免疫化学）。结果显示，PCAD和LAD患者HPG中TET_1、5 mC和5 hmC水平显著升高（P < 0.05）。与此相反，PCAD和LAD患者的HPG中5 fC和5caC水平显著降低（p < 0.05）。总的来说，数据表明在AD临床症状发作之前，易损脑区的甲基化/去甲基化模式改变，这表明在疾病的发病机制中起作用。
The formation of 5-hydroxymethylcytosine (5hmC), a key intermediate of DNA demethylation, is driven by the ten eleven translocation (TET) family of proteins that oxidize 5-methylcytosine (5mC) to 5hmC. To determine whether methylation/demethylation status is altered during the progression of Alzheimer’s disease (AD), levels of TET1, 5mC and subsequent intermediates, including 5hmC, 5-formylcytosine (5fC) and 5-carboxylcytosine (5caC) were quantified in nuclear DNA from the hippocampus/parahippocampal gyrus (HPG) and the cerebellum of 5 age-matched normal controls, 5 subjects with preclinical AD (PCAD) and 7 late-stage AD (LAD) subjects by immunochemistry. The results showed significantly (p < 0.05) increased levels of TET1, 5mC, and 5hmC in the HPG of PCAD and LAD subjects. In contrast, levels of 5fC and 5caC were significantly (p < 0.05) decreased in the HPG of PCAD and LAD subjects. Overall, the data suggest altered methylation/demethylation patterns in vulnerable brain regions prior to the onset of clinical symptoms in AD suggesting a role in the pathogenesis of the disease.
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影响因子：
64.8
作者：
Hajkova, Petra;Ancelin, Katia;Waldmann, Tanja;Lacoste, Nicolas;Lange, Ulrike C.;Cesari, Francesca;Lee, Caroline;Almouzni, Genevieve;Schneider, Robert;Surani, M. Azim
通讯作者：
Surani, M. Azim
影响因子：
6.1
作者：
Aluise CD;Robinson RA;Beckett TL;Murphy MP;Cai J;Pierce WM;Markesbery WR;Butterfield DA
通讯作者：
Butterfield DA
影响因子：
3.7
作者：
Globisch D;Münzel M;Müller M;Michalakis S;Wagner M;Koch S;Brückl T;Biel M;Carell T
通讯作者：
Carell T
Dnmt1 和 Dnmt3a 维持 DNA 甲基化并调节成人前脑神经元的突触功能
影响因子：
25
作者：
Feng, Jian;Zhou, Yu;Campbell, Susan L.;Le, Thuc;Li, En;Sweatt, J. David;Silva, Alcino J.;Fan, Guoping
通讯作者：
Fan, Guoping
影响因子：
3.5
作者：
Fuso, A;Seminara, L;Scarpa, S
通讯作者：
Scarpa, S