International Journal of Molecular Sciences Review Nucleocytoplasmic Transport: Regulatory Mechanisms and the Implications in Neurodegeneration Baojin Ding * and Masood Sepehrimanesh Department of Biology, University of Louisiana at Lafayette, 410 East Saint Mary Boulevard, Lafayette, LA 70503, USA;
[email protected] * Correspondence:
[email protected] Abstract: 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 neurodegener- ation 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. Keywords: Alzheimer’s disease; amyotrophic lateral sclerosis; Huntington disease; neurodegenera- tive diseases; nuclear pore complex; nucleocytoplasmic transport; Ran GTPase Citation: Ding, B.; Sepehrimanesh, M. Nucleocytoplasmic Transport: Regulatory Mechanisms and the Implications in Neurodegeneration. 1. Introduction Int. J. Mol. Sci. 2021, 22, 4165. As a hallmark of eukaryotic cells, the genetic materials are separated from the cyto- https://doi.org/10.3390/ijms plasmic contents by a highly regulated membrane, called nuclear envelope (NE), which 22084165 has two concentric bilayer membranes, the inner nuclear membrane (INM), and outer nuclear membrane (ONM).