Alzheimer's-Focused Administrative Supplement

摘要 核层是与核内膜相邻的中间丝组成的网络，是完整的 所有的后生动物细胞。它在维护核架构方面发挥着关键的结构作用 细胞骨架结构的整合除了有助于基因表达的调节，染色质的定位， 细胞的增殖、迁移和衰老。最近在果蝇模型和阿尔茨海默病模型上的令人兴奋的研究 疾病(AD)的脑组织涉及下调，特别是B型板层蛋白和核骨骼 功能障碍是调节神经退行性变的关键步骤，与阿尔茨海默病(如AD)相关。喇嘛 B1(LB1)是哺乳动物中枢神经系统表达的主要B型层蛋白，该蛋白在发育过程中丢失 导致神经元迁移和皮质组织的严重缺陷。我们建议检验这一假设 LB1在神经元中的过表达可以提供神经保护作用并改善脑缺血再灌注损伤的表型。 Tau介导的小鼠神经变性模型。我们提出的实验将使我们能够测试 耐人寻味的可能性是，调节核层蛋白水平的LB1可以影响一种 Tau介导的阿尔茨海默病小鼠模型的临床相关性

Abstract The nuclear lamina is a meshwork of intermediate filaments adjacent to the inner nuclear membrane, integral to all metazoan cells. It performs a critical structural role in the maintenance of nuclear architecture and integration of cytoskeletal structure in addition to aiding in regulation of gene expression, chromatin positioning, cell proliferation, migration and senescence. Exciting, recent work in Drosophila models and from Alzheimer’s diseases (AD) brain tissue has implicated a down regulation, specifically of B type lamins, and nucleoskeletal dysfunction as a critical step mediating the neurodegeneration associated with tauopathies such as AD. Lamin B1 (LB1) is the major B type lamin expressed in the mammalian CNS and loss of this protein during development results in significant defects in neuronal migration and cortical organization. We propose to test the hypothesis that overexpression of LB1 in neurons can provide a neuroprotective effect and ameliorate the phenotype in a mouse model of tau mediated neurodegeneration. The experiments we have proposed will allow us to test the intriguing possibility that modulating the levels of the nuclear lamina protein, LB1 can impact pathology in a clinically relevant mouse model of tau mediated Alzheimer’s disease