Selective loss of 5hmC promotes neurodegeneration in the mouse model of Alzheimer's disease

	Selective loss of 5hmC promotes neurodegeneration in the mouse model of Alzheimer's disease
	Zhang, Y; Zhang, ZY; Li, LW; Xu, KY; Ma, ZS; Chow, HM; Herrup, K; Li, JL
	2020
发表期刊	FASEB JOURNAL
ISSN	0892-6638
卷号	34 期号:12 页码:16364-16382
摘要	5-hydroxymethylcytosine (5hmC) is an intermediate stage of DNA de-methylation. Its location in the genome also serves as an important regulatory signal for many biological processes and its levels change significantly with the etiology of Alzheimer's disease (AD). In keeping with this relationship, the TET family of enzymes which convert 5-methylcytosine (5mC) to 5hmC are responsive to the presence of A beta. Using hMeDIP-seq, we show that there is a genome-wide reduction of 5hmC that is found in neurons but not in astrocytes from 3xTg mice (an AD mouse model). Decreased TET enzymatic activities in the brains of persons who died with AD suggest that this reduction is the main cause for the loss of 5hmC. Overexpression of human TET catalytic domains (hTETCDs) from the TET family members, especially for hTET3CD, significantly attenuates the neurodegenerative process, including reduced A beta accumulation as well as tau hyperphosphorylation, and improve synaptic dysfunction in 3xTg mouse brain. Our findings define a crucial role of deregulated 5hmC epigenetics in the events leading to AD neurodegeneration.
收录类别	sci
语种	英语
文献类型	期刊论文
条目标识符	http://ir.kiz.ac.cn/handle/152453/13316
专题	科研部门_表观遗传与神经退行性疾病（李家立）
推荐引用方式 GB/T 7714	Zhang, Y,Zhang, ZY,Li, LW,et al. Selective loss of 5hmC promotes neurodegeneration in the mouse model of Alzheimer's disease[J]. FASEB JOURNAL,2020,34(12):16364-16382.
APA	Zhang, Y.,Zhang, ZY.,Li, LW.,Xu, KY.,Ma, ZS.,...&Li, JL.(2020).Selective loss of 5hmC promotes neurodegeneration in the mouse model of Alzheimer's disease.FASEB JOURNAL,34(12),16364-16382.
MLA	Zhang, Y,et al."Selective loss of 5hmC promotes neurodegeneration in the mouse model of Alzheimer's disease".FASEB JOURNAL 34.12(2020):16364-16382.

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