Neuroscience Graduate Program, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA.
Department of Psychology, University of Cincinnati, Cincinnati, Ohio, USA.
Eur J Neurosci. 2022 Sep;56(6):4720-4743. doi: 10.1111/ejn.15791. Epub 2022 Aug 25.
DEK, a chromatin-remodelling phosphoprotein, is associated with various functions and biological pathways in the periphery, including inflammation, oncogenesis, DNA repair, and transcriptional regulation. We recently identified an association between DEK loss and central nervous system diseases, such as Alzheimer's. To understand DEK's potential role in disease, it is critical to characterize DEK in healthy human brain to distinguish between neural DEK expression and function in healthy versus diseased states like dementia. We utilized two public databases, BrainCloud and Human Brain Transcriptome, and analysed DEK mRNA expression across the lifespan in learning and memory relevant brain regions. Since DEK loss induces phenotypes associated with brain ageing (e.g., DNA damage and apoptosis), we hypothesized that neural DEK expression may be highest during foetal development and lower in elderly individuals. In agreement with this hypothesis, DEK was most prominently expressed during foetal development in all queried forebrain areas, relative to other ages. Consistent with its roles in the periphery, pathways related to DEK in the brain were associated with cellular proliferation, DNA replication and repair, apoptosis, and inflammation. We also found novel neural development-relevant pathways (e.g., synaptic transmission, neurite outgrowth, and myelination) to be enriched from genes correlated with DEK expression. These findings suggest that DEK is important for human brain development. Overall, we highlight age-related changes in neural DEK expression across the human lifespan and illuminate novel biological pathways associated with DEK that are distinct from normal brain ageing. These findings may further our understanding of how DEK impacts brain function and disease susceptibility.
DEK 是一种染色质重塑磷酸化蛋白，与外周的各种功能和生物学途径有关，包括炎症、肿瘤发生、DNA 修复和转录调控。我们最近发现 DEK 的缺失与包括阿尔茨海默病在内的中枢神经系统疾病有关。为了了解 DEK 在疾病中的潜在作用，关键是要在健康的人类大脑中对 DEK 进行特征描述，以便将其与痴呆等疾病状态下的神经 DEK 表达和功能区分开来。我们利用了两个公共数据库，即 BrainCloud 和 Human Brain Transcriptome，并分析了与学习和记忆相关的大脑区域中 DEK mRNA 在整个生命周期中的表达。由于 DEK 的缺失会诱导与大脑衰老相关的表型（例如，DNA 损伤和细胞凋亡），我们假设神经 DEK 的表达在胎儿发育期间可能最高，而在老年个体中则较低。与该假说一致，在所有被查询的前脑区域中，DEK 在胎儿发育期间的表达最为显著，而在其他年龄段则较低。与它在周围组织中的作用一致，大脑中的 DEK 相关途径与细胞增殖、DNA 复制和修复、细胞凋亡和炎症有关。我们还发现了与 DEK 表达相关的基因所富集的新的神经发育相关途径（例如，突触传递、轴突生长和髓鞘形成）。这些发现表明 DEK 对人类大脑发育很重要。总体而言，我们强调了在人类生命周期中神经 DEK 表达随年龄的变化，并阐明了与 DEK 相关的新的生物学途径，这些途径与正常的大脑衰老不同。这些发现可能有助于我们进一步了解 DEK 如何影响大脑功能和疾病易感性。
