Figure 5. Cellular aging, disease, and nucleocytoplasmic transport.
The dysfunction of nucleocytoplasmic transport is observed during aging and neurodegenerative diseases. Age-related transcriptome changes, in particular the downregulation of nuclear transport factors (e.g., karyopherins and RanBP1), lead to dysfunction of nucleocytoplasmic transport that results in the accumulation and aggregation of proteins in the cytoplasm. Cytosolic aggregates, in turn, cause structural abnormalities in the NPCs and further compromise nuclear import and export of proteins and mRNAs. Disease-associated proteins take the same route as aging to target and perturb the function of the NPC.