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. Author manuscript; available in PMC: 2023 Mar 15.
Published in final edited form as: Nat Rev Neurol. 2022 Apr 29;18(6):348–362. doi: 10.1038/s41582-022-00653-6

Fig. 3 |. Pathological progression of changes to the nuclear pore complex and nucleocytoplasmic transport in amyotrophic lateral sclerosis.

Fig. 3 |

Aberrant nuclear retention of the ESCRT-III-associated protein CHMP7 initiates nuclear pore injury characterized by the reduction in specific nucleoporins (Nups) from the nuclear pore complex (NPC), leading to an altered composition of the NPC (1). Disruption of the NPC in this way alters functional nucleocytoplasmic transport (NCT) (2), which ultimately leads to loss of TAR DNA-binding protein 43 (TDP43) function within the nucleus and translocation of TDP43 from the nucleus to the cytoplasm (3). Impaired NCT might result in cytoplasmic accumulation of TDP43, Nups and nuclear transport receptors in end-stage disease (4). Impaired nuclear import might then inhibit restoration of the NPC composition and integrity (5), thereby exacerbating the process.