Nuclear pore destruction and loss of nuclear TDP-43 in FUS mutation-related amyotrophic lateral sclerosis motor neurons

Nuclear pore complexes (NPCs) are localized throughout the nuclear envelope and play a pivotal role in regulating nucleocytoplasmic transport, which is critical for the function of all eukaryotic cells. NPCs deteriorate age-dependently, and this is associated with increased nuclear permeability. The disruption of NPCs has been observed in several neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS), which can present in several ways, including sporadic, SOD1-related, C9orf72-related, and fused in sarcoma (FUS)-related ALS [ [1] Lin Y.C. Kumar M.S. Ramesh N. Anderson E.N. Nguyen A.T. Kim B. et al. Interactions between ALS-linked FUS and nucleoporins are associated with defects in the nucleocytoplasmic transport pathway. Nat. Neurosci. 2021; 24: 1077-1088https://doi.org/10.1038/s41593-021-00859-9 Google Scholar ]. However, the altered expression of nucleoporins and 43-kDa TAR DNA-binding protein (TDP-43) in FUS mutation-related ALS motor neurons remains unclear.