Frontiers in Molecular Neuroscience ( IF 3.5 ) Pub Date : 2020-10-20 , DOI: 10.3389/fnmol.2020.594319 Allie N Greene 1 , Lois G Parks 2 , Matia B Solomon 1, 3 , Lisa M Privette Vinnedge 2, 4
Alzheimer’s disease (AD) is the most common cause of dementia and is characterized by the buildup of β-amyloid plaques and neurofibrillary Tau tangles. This leads to decreased synaptic efficacy, cell death, and, consequently, brain atrophy in patients. Behaviorally, this manifests as memory loss and confusion. Using a gene ontology analysis, we recently identified AD and other age-related dementias as candidate diseases associated with the loss of DEK expression. DEK is a nuclear phosphoprotein with roles in DNA repair, cellular proliferation, and inhibiting apoptosis. Work from our laboratory determined that DEK is highly expressed in the brain, particularly in regions relevant to learning and memory, including the hippocampus. Moreover, we have also determined that DEK is highly expressed in neurons. Consistent with our gene ontology analysis, we recently reported that cortical DEK protein levels are inversely proportional to dementia severity scores in elderly female patients. However, the functional role of DEK in neurons is unknown. Thus, we knocked down DEK in an
中文翻译:
DEK 表达的缺失诱导分化的 SH-SY5Y 细胞中的阿尔茨海默病表型
阿尔茨海默病 (AD) 是痴呆的最常见原因,其特征是 β-淀粉样蛋白斑块和神经原纤维 Tau 缠结的积累。这导致突触功效降低、细胞死亡,从而导致患者脑萎缩。在行为上,这表现为记忆丧失和混乱。使用基因本体分析,我们最近将 AD 和其他与年龄相关的痴呆确定为与 DEK 表达丧失相关的候选疾病。DEK 是一种核磷蛋白,在 DNA 修复、细胞增殖和抑制细胞凋亡中发挥作用。我们实验室的工作确定 DEK 在大脑中高度表达,特别是在与学习和记忆相关的区域,包括海马体。此外,我们还确定 DEK 在神经元中高度表达。与我们的基因本体分析一致,我们最近报道了皮质 DEK 蛋白水平与老年女性患者的痴呆严重程度评分成反比。然而,DEK 在神经元中的功能作用尚不清楚。因此,我们击倒了 DEK