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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• 作者：A. Iatrou ; G. Kenis ; B. P. F. Rutten ; K. Lunnon…
• 关键词：Alzheimer’s disease ; Locus coeruleus ; Raphe nuclei ; Epigenetics ; DNA methylation ; DNA hydroxymethylation
• 刊名：Cellular and Molecular Life Sciences
• 出版年：2017
• 出版时间：February 2017
• 年：2017
• 卷：74
• 期：3
• 页码：509-523
• 全文大小：573KB
• 刊物类别：Biomedical and Life Sciences
• 刊物主题：Cell Biology; Biomedicine, general; Life Sciences, general; Biochemistry, general;
• 出版者：Springer International Publishing
• ISSN：1420-9071
• 卷排序：74

文摘

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.