Nuclear pore complexes — a doorway to neural injury in neurodegeneration
Open accessAbstract
The genetic underpinnings and end-stage pathological hallmarks of neurodegenerative diseases are increasingly well defined, but the cellular pathophysiology of disease initiation and propagation remains poorly understood, especially in sporadic forms of these diseases. Altered nucleocytoplasmic transport is emerging as a prominent pathomechanism of multiple neurodegenerative diseases, including amyotrophic lateral sclerosis, Alzheimer disease, frontotemporal dementia and Huntington disease. The nuclear pore complex (NPC) and interactions between its individual nucleoporin components and nuclear transport receptors regulate nucleocytoplasmic transport, as well as genome organization and gene expression. Specific nucleoporin abnormalities have been identified in sporadic and familial forms of neurodegenerative disease, and these alterations are thought to contribute to disrupted nucleocytoplasmic transport. The specific nucleoporins and nucleocytoplasmic transport proteins that have been linked to different neurodegenerative diseases are partially distinct, suggesting that NPC injury contributes to the cellular specificity of neurodegenerative disease and could be an early initiator of the pathophysiological cascades that underlie neurodegenerative disease. This concept is consistent with the fact that rare genetic mutations in some nucleoporins cause cell-type-specific neurological disease. In this Review, we discuss nucleoporin and NPC disruptions and consider their impact on cellular function and the pathophysiology of neurodegenerative disease.
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Cell lines 1021 and 793 are control lines, and 883 and 321 are C9ORF lines.
“The cell lines 1021 and 793 (controls) and 883 and 321 (C9ORF) were generated and characterized as previously described (7).”
From Nemo-like kinase disrupts nuclear import and drives TDP43 mislocalization in ALS (2025) · cites this paper as [7]
The ‘Nucleocytoplasmic transport alterations’ section discusses C9orf72 iPSC-derived neurons, but does not identify cell lines 1021, 793, 883, or 321. Searches for those identifiers and for the lines’ generation and characterization found no confirming passage in our copy. (LLM, conf=0.75)
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Nuclear proteasomes buffer cytoplasmic proteins during autophagy compromise
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Nuclear mechanics as a determinant of nuclear pore complex plasticity
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Ibetazol, a novel inhibitor of importin β1-mediated nuclear import
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Protein quality control systems in neurodegeneration – culprits, mitigators, and solutions?
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Karyopherins remodel the dynamic organization of the nuclear pore complex transport barrier
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Changing the guard—nuclear pore complex quality control
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Protein folding and quality control during nuclear transport
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Exploring dysregulated miRNAs in ALS: implications for disease pathogenesis and early diagnosis
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The cochlea is built to last a lifetime
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Cytoplasmic nucleoporin assemblage: the cellular artwork in physiology and disease
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Physical model of the nuclear membrane permeability mechanism
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Nanoimaging of SARS-CoV-2 viral invasion toward the nucleus and genome
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RanBP2-dependent annulate lamellae drive nuclear pore assembly and nuclear expansion
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POCT devices for neurodegenerative disorders: from lab to clinics
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Accelerated neuronal aging in vitro ∼melting watch ∼
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Machine learning approaches based on fibroblast morphometry do not predict ALS
Woo, E., Bredvik, K. G., Liu, B., Fuchs, T. J., Manfredi, G., & Konràd, C. (2023) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2023.06.010 · Cited by 4 · see citing works
From Blur to Brilliance: The Ascendance of Advanced Microscopy in Neuronal Cell Biology
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Nucleoporin Nup358 Downregulation Tunes the Neuronal Excitability in Mouse Cortical Neurons
Martínez-Rojas, V. A., Pischedda, F., Romero-Maldonado, I., Khalaf, B., Piccoli, G., Macchi, P., & Musio, C. (2023) · Life · doi:10.3390/life13091791 · Cited by 3 · see citing works
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Uniquome: Construction and decoding of a novel proteomic atlas that contains new peptide entities
Kontopodis, E., Pierros, V., Vorgias, C. E., Papassideri, I. S., Stravopodis, D. J., & Tsangaris, G. T. (2025) · Computational and Structural Biotechnology Journal · doi:10.1016/j.csbj.2025.05.027 · Cited by 3 · see citing works
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Sequence features and dynamics of subcellular translation revealed by APEX-Ribo-SeqPreprint
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Nemo-like kinase disrupts nuclear import and drives TDP43 mislocalization in ALS
Bekier, M. E., Pinarbasi, E., Krishnan, G., Mesojedec, J. J., Hurley, M., Harikumar Sheela, H., Collins, C. A., Ghaffari, L., de Majo, M., Ullian, E. M., et al. (2025) · Journal of Clinical Investigation · doi:10.1172/jci188138 · Cited by 2 · see citing works
“The cell lines 1021 and 793 (controls) and 883 and 321 (C9ORF) were generated and characterized as previously described (7).”
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Amperometric ion-selective nanoelectrodes for bioanalytical sensing and imaging
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Small extrachromosomal circular DNA in amyotrophic lateral sclerosis matter
Araúzo-Bravo, M. J., Daniela Gerovska, D., Schwab, M. G., & Kretz, A. (2024) · Neural Regeneration Research · doi:10.4103/nrr.nrr-d-23-01877 · Cited by 2 · see citing works
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Özışık, O., Kara, N. S., Abbassi‐Daloii, T., Térézol, M., Kuijper, E. C., Queralt-Rosiñach, N., Jacobsen, A., Sezerman, O. U., Roos, M., Evelo, C. T., et al. (2025) · Scientific Reports · doi:10.1038/s41598-025-85580-4 · Cited by 1 · see citing works
Aberrant nuclear pore complex degradation contributes to neurodegeneration in VCP disease
Dubey, S. K., Chaubey, D., Ikenaga, C., Lin, W.-W., Bellen, H. J., & Lloyd, T. E. (2025) · Neuron · doi:10.1016/j.neuron.2025.11.017 · Cited by 1 · see citing works
Impaired nucleocytoplasmic transport in SOD1-mediated ALS
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RNA export through the nuclear pore complex: pathways, mechanisms, and imaging strategies
Fu, D., Yu, W., Zhang, F., Rush, C., Tingey, M., & Yang, W. (2026) · RNA Biology · doi:10.1080/15476286.2026.2656571 · Cited by 1 · see citing works
Annulate lamellae – an underexplored cellular structure
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Bonde, L. D., Hecher, L., Alawi, M., Forbes, K. P. N., Symonds, J. D., Hamilton, M., & Kutsche, K. (2025) · Journal of Medical Genetics · doi:10.1136/jmg-2025-110671 · Cited by 1 · see citing works
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Harkness, J. R., McDermott, J. H., Marsden, S., Jamieson, P., Metcalfe, K., Khan, N., Macken, W. L., Pitceathly, R. D. S., Record, C. J., Maroofian, R., et al. (2025) · The Lancet Neurology · doi:10.1016/s1474-4422(25)00198-x · Cited by 1 · see citing works
Imaging-Based Quantitative Assessment of Biomolecular Condensates in vitro and in CellsPreprint
Bergsma, T., Steen, A., Kamenz, J. L., Gallardo, P., & Veenhoff, L. M. (2024) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2024.05.22.594518 · Cited by 1 · see citing works
Asymmetric centromere and gene locus positioning in Drosophila neural stem cellsPreprint
Taylor, J. A., & Cabernard, C. (2025) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2025.09.14.676095 · Cited by 1 · see citing works
Solomon, D. A., Emenecker, R. J., Salcher-Konrad, M.-T., Konstantinidou, S. M., Houghton, O. H., Wycherley, E., Lee, S., O’Brien, N. L., Alcalde, J., Cabaco, I. L., et al. (2026) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.64898/2026.03.16.711670 · Cited by 1 · see citing works
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Özışık, O., Kara, N. S., Abbassi‐Daloii, T., Térézol, M., Queralt-Rosiñach, N., Jacobsen, A., Sezerman, O. U., Roos, M., Evelo, C. T., Baudot, A., et al. (2023) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2023.07.22.550153
Theme 05 - Human Cell Biology and Pathology
(2023) · Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration · doi:10.1080/21678421.2023.2260195
Wang, H., Chen, G., & Zhang, Z. (2025) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2025.05.28.656622
When children diagnosed with Guillain-Barré syndrome do not recover
de Wit, M. Y., & Jacobs, B. C. (2025) · The Lancet Neurology · doi:10.1016/s1474-4422(25)00240-6
Decoding ATXN2 Phosphocode: Structural Insights and Therapeutic Opportunities in Disease
Kumar, A. P. K. A., Subair, S., Shivamurthy, P. B., Ummar, S., Rajeev, A. C., & Raju, R. (2025) · The Protein Journal · doi:10.1007/s10930-025-10287-4
Amperometric Ion-Selective Nanoelectrodes for Bioanalytical Sensing and ImagingPreprint
Amemiya, S., & Kim, J. (2025) · SSRN Electronic Journal · doi:10.2139/ssrn.5806924
Cline, B. T., Torrice, C., Fan, W. Y., Addish, S. A., Hazelbaker, M. A., Bear, J. E., & Cho, U. H. (2025) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.64898/2025.12.04.692439
AutoSTED: An automated workflow for STED super-resolution imaging of cell nucleiPreprint
Leger, D., Ivanisevic, M., & Lénárt, P. (2025) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.64898/2025.12.11.693650
Han, M., Ge, S., Zhao, G., Yang, P., Luo, Z., Qian, C., Pan, L., Fu, P., Xu, T., & Chen, Z. (2026) · Research Square · doi:10.21203/rs.3.rs-9224000/v1
Myelin basic protein is an RNA chaperone in microglial nuclear retro-transportPreprint
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The love and hate relationship between cellular senescence and stemness
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Mechanoresponsive modulation of nuclear pore complex structure and function by O -GlcNAcPreprint
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Napoletano, F. (2026) · Frontiers in Cell Death · doi:10.3389/fceld.2026.1954383
Parandhaman, M., Huang, S.-H., Dzurik, K. G., Childers, W. S., & Amemiya, S. (2026) · Analytical Chemistry · doi:10.1021/acs.analchem.6c04319
Microtubules and nuclear pores position centromeres and genes in neural stem cells
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- Authors
- Coyne, A. N., & Rothstein, J. D.
- Affiliations
- Johns Hopkins University (US)
- Corresponding author
- Coyne, Alyssa N.
- Rothstein, Jeffrey D.
- Venue
- Nature Reviews Neurology
- Published
- 2022-04-29
- Volume
- 18
- Issue
- 6
- Pages
- 348-362
- ISSN
- 1759-4758 (ISSN-L)
- 1759-4766
- PMC
- PMC10015220
- OpenAlex
- W4225109825
- Cited by
- 96
- References
- 188
- Citations by year
- 2026: 16 · 2025: 24 · 2024: 28 · 2023: 24 · 2022: 4
- FWCI
- 2.08
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Nature Reviews Neurology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- U.S. Department of Defense
- Muscular Dystrophy Association
- National Institutes of Health
- National Institute of Neurological Disorders and Stroke (P01NS099114, K99NS123242, P01NS084974, R01NS094239, R01NS122236)
- Robert Packard Center for ALS Research, Johns Hopkins University
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nuclear Structure and Function
- Health Sciences › Medicine › Neurology › Amyotrophic Lateral Sclerosis Research
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Hereditary Neurological Disorders
- Keywords
- nuclear pore complex, nucleoporins, nuclear transport, neurodegenerative diseases, amyotrophic lateral sclerosis, Alzheimer's disease, frontotemporal dementia, Huntington's disease, nuclear transport receptors, genetic mutations
- MeSH terms
- Humans, Neurodegenerative Diseases, Active Transport, Cell Nucleus, Nuclear Pore, Nuclear Pore Complex Proteins, Frontotemporal Dementia
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