Into the Fourth Dimension: Dysregulation of Genome Architecture in Aging and Alzheimer's Disease.
Into the Fourth Dimension: Dysregulation of Genome Architecture in Aging and Alzheimer's Disease.
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DOI：
10.3389/fnmol.2018.00060
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发表时间：
2018
影响因子：
4.8
通讯作者：
Rylett RJ
中科院分区：
文献类型：
--
作者：
Winick-Ng W;Rylett RJ
阿尔茨海默病（AD）是一种进行性神经退行性疾病，其特征是突触功能障碍和认知障碍。了解 AD 的发生和进展具有挑战性，因为该疾病高度复杂且涉及多因素。环境和遗传因素在 AD 发病机制中都发挥着重要作用，单基因水平上复杂 DNA 修饰的观察以及新证据也表明 AD 患者基因组结构的变化凸显了这一点。染色质在空间和时间上的四维结构对于有丝分裂后神经元基因表达的上下文依赖性调节至关重要。在衰老的大脑和 AD 患者中观察到表观遗传过程的失调，尽管这些变化对转录的影响尚未达成一致。新的证据表明，参与基因组组织的蛋白质已经改变了 AD 大脑中的表达和定位，这表明基因组景观可能在 AD 的发展中发挥着关键作用。这篇综述讨论了染色质组织者和表观遗传修饰剂在有丝分裂后细胞、衰老大脑以及 AD 发生和进展中的作用。还将讨论如何利用这些新见解来帮助确定疾病风险并为治疗策略提供信息。
Alzheimer’s disease (AD) is a progressive neurodegenerative disease characterized by synapse dysfunction and cognitive impairment. Understanding the development and progression of AD is challenging, as the disease is highly complex and multifactorial. Both environmental and genetic factors play a role in AD pathogenesis, highlighted by observations of complex DNA modifications at the single gene level, and by new evidence that also implicates changes in genome architecture in AD patients. The four-dimensional structure of chromatin in space and time is essential for context-dependent regulation of gene expression in post-mitotic neurons. Dysregulation of epigenetic processes have been observed in the aging brain and in patients with AD, though there is not yet agreement on the impact of these changes on transcription. New evidence shows that proteins involved in genome organization have altered expression and localization in the AD brain, suggesting that the genomic landscape may play a critical role in the development of AD. This review discusses the role of the chromatin organizers and epigenetic modifiers in post-mitotic cells, the aging brain, and in the development and progression of AD. How these new insights can be used to help determine disease risk and inform treatment strategies will also be discussed.
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影响因子：
3.7
作者：
Angrand PO;Vennin C;Le Bourhis X;Adriaenssens E
通讯作者：
Adriaenssens E
DOI：
10.1523/jneurosci.3583-12.2012
发表时间：
2012-12-05
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Close J;Xu H;De Marco García N;Batista-Brito R;Rossignol E;Rudy B;Fishell G
通讯作者：
Fishell G
影响因子：
82.9
作者：
Alonso, AD;GrundkeIqbal, I;Iqbal, K
通讯作者：
Iqbal, K
影响因子：
4.5
作者：
Babiarz, Joshua E.;Hsu, Ruby;Blelloch, Robert
通讯作者：
Blelloch, Robert
影响因子：
5.3
作者：
Balamotis, Michael A.;Tamberg, Nele;Kohwi, Yoshinori
通讯作者：
Kohwi, Yoshinori