Neurons in Vulnerable Regions of the Alzheimer's Disease Brain Display Reduced ATM Signaling
文献类型：期刊论文
| 作者 | Shen XT1,2; Chen JM3; Li JL4; Julia Kofler5; Karl Herrup[*]1 |
| 刊名 | eNeuro
 |
| 出版日期 | 2016 |
| 卷号 | 3期号:1页码:e0124-15 |
| 关键词 | ataxia-telangiectasia cell cycle EZH2 HDAC4 neurodegeneration |
| 通讯作者 | herrup@ust.hk |
| 英文摘要 | Ataxia telangiectasia (A-T) is a multisystemic disease caused by mutations in the ATM (A-T mutated) gene. It strikes before 5 years of age and leads to dysfunctions in many tissues, including the CNS, where it leads to neurodegeneration, primarily in cerebellum. Alzheimer's disease (AD), by contrast, is a largely sporadic neurodegenerative disorder that rarely strikes before the 7th decade of life with primary neuronal losses in hippocampus, frontal cortex, and certain subcortical nuclei. Despite these differences, we present data supporting the hypothesis that a failure of ATM signaling is involved in the neuronal death in individuals with AD. In both, partially ATM-deficient mice and AD mouse models, neurons show evidence for a loss of ATM. In human AD, three independent indices of reduced ATM function-nuclear translocation of histone deacetylase 4, trimethylation of histone H3, and the presence of cell cycle activity-appear coordinately in neurons in regions where degeneration is prevalent. These same neurons also show reduced ATM protein levels. And though they represent only a fraction of the total neurons in each affected region, their numbers significantly correlate with disease stage. This previously unknown role for the ATM kinase in AD pathogenesis suggests that the failure of ATM function may be an important contributor to the death of neurons in AD individuals. |
| 收录类别 | 其他 |
| 资助信息 | This work was supported by the Research Grants Counsel of Hong Kong (Grants GRF660813, HKSAR and HKUST12/CRF/13G), the National Institutes of Health (Grants NS70193), and the National Key Basic Research Program of China (2013CB530900) to K.H. Support was also received from the University of Pittsburgh Alzheimer’s Disease Research Center Brain Bank (Grant P50 AG005133), the Washington University in St. Louis Alzheimer’s Disease Re- search Center (Grant P50 AG05681), and the BrightFocus Foundation (Grants 100006312 and A2012101). |
| 语种 | 英语 |
| 源URL | [http://159.226.149.26:8080/handle/152453/9647]  |
| 专题 | 昆明动物研究所_表观遗传与神经退行性疾病 昆明动物研究所_动物模型与人类重大疾病机理重点实验室 |
| 作者单位 | 1.Division of Life Science, Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong, China 2.Department of Otolaryngology, Xiangya Hospital, Central South University, Changsha 410008, Hunan, China, 3.Department of Cell Biology and Neuroscience, Rutgers University, Piscataway, New Jersey 08854 4.Key Laboratory of Animal Models and Human Disease Mechanisms of Chinese Academy of Sciences, and Yunnan Province, Kunming Institute of Zoology, Kunming 650223, Yunnan, China 5.Department of Pathology and The Alzheimer’s Disease Research Center, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15213 |
| 推荐引用方式 GB/T 7714 | Shen XT,Chen JM,Li JL,et al. Neurons in Vulnerable Regions of the Alzheimer's Disease Brain Display Reduced ATM Signaling[J]. eNeuro,2016,3(1):e0124-15. |
| APA | Shen XT,Chen JM,Li JL,Julia Kofler,&Karl Herrup[*].(2016).Neurons in Vulnerable Regions of the Alzheimer's Disease Brain Display Reduced ATM Signaling.eNeuro,3(1),e0124-15. |
| MLA | Shen XT,et al."Neurons in Vulnerable Regions of the Alzheimer's Disease Brain Display Reduced ATM Signaling".eNeuro 3.1(2016):e0124-15. |
入库方式： OAI收割
来源：昆明动物研究所
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