Epigenetic dysregulation of brainstem nuclei in the pathogenesis of Alzheimer's disease: looking in the correct place at the right time?
Epigenetic dysregulation of brainstem nuclei in the pathogenesis of Alzheimer's disease: looking in the correct place at the right time?
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DOI：
10.1007/s00018-016-2361-4
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发表时间：
2017-02
期刊：
影响因子：
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通讯作者：
van den Hove DL
中科院分区：
文献类型：
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作者：
Iatrou A;Kenis G;Rutten BP;Lunnon K;van den Hove DL
尽管阿尔茨海默病(AD)的病因尚不清楚，但有人认为遗传、表观遗传和环境因素之间存在相互作用。越来越多的证据表明，表观遗传机制中的失调在阿尔茨海默病中发挥了作用。基因组技术的最新发展使得对表观基因组的高通量询问成为可能，表观基因组范围的关联研究已经确定了大脑皮层AD的独特表观遗传学特征。大量证据表明，脑干早期的调节失调，尤其是在中缝核团和蓝斑，是最早期的非认知症状，表明AD的发病机制可能存在因果关系。在这里，我们回顾了表观基因组学技术的进展及其在AD研究领域的应用，特别是与脑干的相关性。在这方面，我们建议评估脑干中的表观遗传特征作为询问AD因果关系的基石。了解脑干中的表观遗传失调如何导致AD易感性，对于了解疾病的病因和开发新的诊断和治疗策略至关重要。
Even though the etiology of Alzheimer’s disease (AD) remains unknown, it is suggested that an interplay among genetic, epigenetic and environmental factors is involved. An increasing body of evidence pinpoints that dysregulation in the epigenetic machinery plays a role in AD. Recent developments in genomic technologies have allowed for high throughput interrogation of the epigenome, and epigenome-wide association studies have already identified unique epigenetic signatures for AD in the cortex. Considerable evidence suggests that early dysregulation in the brainstem, more specifically in the raphe nuclei and the locus coeruleus, accounts for the most incipient, non-cognitive symptomatology, indicating a potential causal relationship with the pathogenesis of AD. Here we review the advancements in epigenomic technologies and their application to the AD research field, particularly with relevance to the brainstem. In this respect, we propose the assessment of epigenetic signatures in the brainstem as the cornerstone of interrogating causality in AD. Understanding how epigenetic dysregulation in the brainstem contributes to AD susceptibility could be of pivotal importance for understanding the etiology of the disease and for the development of novel diagnostic and therapeutic strategies.