Department of Biology, University of Louisiana at Lafayette, 410 East Saint Mary Boulevard, Lafayette, LA 70503, USA.
Int J Mol Sci. 2021 Apr 17;22(8):4165. doi: 10.3390/ijms22084165.
Nucleocytoplasmic transport (NCT) across the nuclear envelope is precisely regulated in eukaryotic cells, and it plays critical roles in maintenance of cellular homeostasis. Accumulating evidence has demonstrated that dysregulations of NCT are implicated in aging and age-related neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS), frontotemporal dementia (FTD), Alzheimer's disease (AD), and Huntington disease (HD). This is an emerging research field. The molecular mechanisms underlying impaired NCT and the pathogenesis leading to neurodegeneration are not clear. In this review, we comprehensively described the components of NCT machinery, including nuclear envelope (NE), nuclear pore complex (NPC), importins and exportins, RanGTPase and its regulators, and the regulatory mechanisms of nuclear transport of both protein and transcript cargos. Additionally, we discussed the possible molecular mechanisms of impaired NCT underlying aging and neurodegenerative diseases, such as ALS/FTD, HD, and AD.
核质转运（NCT）穿过核膜在真核细胞中受到精确调控，它在维持细胞内稳态方面发挥着关键作用。越来越多的证据表明，NCT 的失调与衰老和与年龄相关的神经退行性疾病有关，包括肌萎缩侧索硬化症（ALS）、额颞叶痴呆（FTD）、阿尔茨海默病（AD）和亨廷顿病（HD）。这是一个新兴的研究领域。导致 NCT 受损和神经退行性病变的发病机制尚不清楚。在这篇综述中，我们全面描述了 NCT 机制的组成部分，包括核膜（NE）、核孔复合物（NPC）、导入蛋白和输出蛋白、RanGTPase 及其调节剂，以及蛋白质和转录物货物的核转运的调节机制。此外，我们还讨论了 NCT 受损与衰老和神经退行性疾病（如 ALS/FTD、HD 和 AD）之间可能的分子机制。
