C9orf72 poly(GR) aggregation induces TDP-43 proteinopathy

Ubiquitinated TDP-43 in Frontotemporal Lobar Degeneration and Amyotrophic Lateral Sclerosis

Neumann, M., Sampathu, D. M., Kwong, L. K., Truax, A. C., Micsenyi, M. C., Chou, T. T., Bruce, J., Schuck, T., Grossman, M., Clark, C. M., et al. (2006) · Science · doi:10.1126/science.1134108 · Cited by 6,576

Expanded GGGGCC Hexanucleotide Repeat in Noncoding Region of C9ORF72 Causes Chromosome 9p-Linked FTD and ALS

DeJesus-Hernandez, M., Mackenzie, I. R., Boeve, B. F., Boxer, A. L., Baker, M., Rutherford, N. J., Nicholson, A. M., Finch, N. A., Flynn, H., Adamson, J., et al. (2011) · Neuron · doi:10.1016/j.neuron.2011.09.011 · Cited by 4,936

A Hexanucleotide Repeat Expansion in C9ORF72 Is the Cause of Chromosome 9p21-Linked ALS-FTD

Renton, A. E., Majounie, E., Waite, A., Simón-Sánchez, J., Rollinson, S., Gibbs, J. R., Schymick, J. C., Laaksovirta, H., van Swieten, J. C., Myllykangas, L., et al. (2011) · Neuron · doi:10.1016/j.neuron.2011.09.010 · Cited by 4,409

TDP-43 is a component of ubiquitin-positive tau-negative inclusions in frontotemporal lobar degeneration and amyotrophic lateral sclerosis

Arai, T., Hasegawa, M., Akiyama, H., Ikeda, K., Nonaka, T., Mori, H., Mann, D., Tsuchiya, K., Yoshida, M., Hashizume, Y., et al. (2006) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2006.10.093 · Cited by 2,732

Ataxin-2 intermediate-length polyglutamine expansions are associated with increased risk for ALS

Elden, A. C., Kim, H.-J., Hart, M. P., Chen‐Plotkin, A. S., Johnson, B. S., Fang, X., Armakola, M., Geser, F., Greene, R. A., Lu, M. M., et al. (2010) · Nature · doi:10.1038/nature09320 · Cited by 1,361

Neurofilament light chain as a biomarker in neurological disorders

Gaetani, L., Blennow, K., Calabresi, P., Di Filippo, M., Parnetti, L., & Zetterberg, H. (2019) · Journal of Neurology, Neurosurgery & Psychiatry · doi:10.1136/jnnp-2018-320106 · Cited by 1,334

The C9orf72 GGGGCC Repeat Is Translated into Aggregating Dipeptide-Repeat Proteins in FTLD/ALS

Mori, K., Weng, S., Arzberger, T., May, S., Rentzsch, K., Kremmer, E., Schmid, B., Kretzschmar, H. A., Cruts, M., Broeckhoven, C. V., et al. (2013) · Science · doi:10.1126/science.1232927 · Cited by 1,248

Unconventional Translation of C9ORF72 GGGGCC Expansion Generates Insoluble Polypeptides Specific to c9FTD/ALS

Ash, P. E. A., Bieniek, K. F., Gendron, T. F., Caulfield, T. R., Lin, W.-L., DeJesus‐Hernandez, M., van Blitterswijk, M., Jansen‐West, K. R., Paul, J. W., Rademakers, R., et al. (2013) · Neuron · doi:10.1016/j.neuron.2013.02.004 · Cited by 1,127

The C9orf72 repeat expansion disrupts nucleocytoplasmic transport.

Zhang, K., Donnelly, C. J., Haeusler, A. R., Grima, J. C., Machamer, J. B., Steinwald, P., Daley, E. L., Miller, S. J., Cunningham, K. M., Vidensky, S., et al. (2015) · Nature · doi:10.1038/nature14973 · Cited by 982

GGGGCC repeat expansion in C9orf72 compromises nucleocytoplasmic transport

Freibaum, B. D., Lu, Y., Lopez-Gonzalez, R., Kim, N. C., Almeida, S., Lee, K.-H., Badders, N., Valentine, M., Miller, B. L., Wong, P. C., et al. (2015) · Nature · doi:10.1038/nature14974 · Cited by 841

TDP-43 Is Intrinsically Aggregation-prone, and Amyotrophic Lateral Sclerosis-linked Mutations Accelerate Aggregation and Increase Toxicity

Johnson, B. S., Snead, D., Lee, J. J., McCaffery, J. M., Shorter, J., & Gitler, A. D. (2009) · Journal of Biological Chemistry · doi:10.1074/jbc.m109.010264 · Cited by 812

RAN proteins and RNA foci from antisense transcripts in C9ORF72 ALS and frontotemporal dementia

Zu, T., Liu, Y., Báñez-Coronel, M., Reid, T. S., Pletniková, O., Lewis, J. M., Miller, T. M., Harms, M. B., Falchook, A. E., Subramony, S. H., et al. (2013) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1315438110 · Cited by 777

Characterization and Functional Implications of the RNA Binding Properties of Nuclear Factor TDP-43, a Novel Splicing Regulator ofCFTR Exon 9

Buratti, E., & Baralle, F. E. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m104236200 · Cited by 697

C9orf72 Dipeptide Repeats Impair the Assembly, Dynamics, and Function of Membrane-Less Organelles

Lee, K., Zhang, P., Kim, H. J., Mitrea, D. M., Sarkar, M., Freibaum, B. D., Cika, J., Coughlin, M., Messing, J., Molliex, A., et al. (2016) · Cell · doi:10.1016/j.cell.2016.10.002 · Cited by 691

Aberrant cleavage of TDP-43 enhances aggregation and cellular toxicity

Zhang, Y., Xu, Y.-F., Cook, C. N., Gendron, T. F., Roettges, P. S., Link, C. D., Lin, W.-L., Tong, J., Castanedes‐Casey, M., Ash, P. E. A., et al. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0900688106 · Cited by 614

Modifiers of C9orf72 dipeptide repeat toxicity connect nucleocytoplasmic transport defects to FTD/ALS

Jovičić, A., Mertens, J., Boeynaems, S., Bogaert, E., Chai, N., Yamada, S. B., Paul, J. W., Sun, S., Herdy, J. R., Bieri, G., et al. (2015) · Nature Neuroscience · doi:10.1038/nn.4085 · Cited by 598

Targeted degradation of sense and antisense C9orf72 RNA foci as therapy for ALS and frontotemporal degeneration

Lagier‐Tourenne, C., Baughn, M. W., Rigo, F., Sun, S., Liu, P., Li, H., Jiang, J., Watt, A. T., Chun, S. J., Katz, M., et al. (2013) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1318835110 · Cited by 585

Antisense transcripts of the expanded C9ORF72 hexanucleotide repeat form nuclear RNA foci and undergo repeat-associated non-ATG translation in c9FTD/ALS

Gendron, T. F., Bieniek, K. F., Zhang, Y., Jansen‐West, K. R., Ash, P. E. A., Caulfield, T. R., Daughrity, L. M., Dunmore, J., Castanedes‐Casey, M., Chew, J., et al. (2013) · Acta Neuropathologica · doi:10.1007/s00401-013-1192-8 · Cited by 569

RNA Binding Antagonizes Neurotoxic Phase Transitions of TDP-43

Mann, J. R., Gleixner, A. M., Mauna, J. C., Gomes, E., DeChellis-Marks, M. R., Needham, P. G., Copley, K. E., Hurtle, B. T., Portz, B., Pyles, N. J., et al. (2019) · Neuron · doi:10.1016/j.neuron.2019.01.048 · Cited by 547

Gain of toxicity from ALS/FTD-linked repeat expansions in C9ORF72 is alleviated by antisense oligonucleotides targeting GGGGCC-containing RNAs

Jiang, J., Zhu, Q., Gendron, T. F., Saberi, S., McAlonis-Downes, M., Seelman, A., Stauffer, J. E., Jafar-nejad, P., Drenner, K., Schulte, D., et al. (2016) · Neuron · doi:10.1016/j.neuron.2016.04.006 · Cited by 536

Cytoplasmic TDP-43 De-mixing Independent of Stress Granules Drives Inhibition of Nuclear Import, Loss of Nuclear TDP-43, and Cell Death

Gasset-Rosa, F., Lu, S., Yu, H., Chen, C., Melamed, Z., Guo, L. E., Shorter, J., Cruz, S. D., & Cleveland, D. W. (2019) · Neuron · doi:10.1016/j.neuron.2019.02.038 · Cited by 526

Phase Separation of C9orf72 Dipeptide Repeats Perturbs Stress Granule Dynamics

Boeynaems, S., Bogaert, E., Kovács, D., Konijnenberg, A., Timmerman, E., Volkov, A. N., Guharoy, M., Decker, M. D., Jaspers, T., Ryan, V. H., et al. (2017) · Molecular Cell · doi:10.1016/j.molcel.2017.02.013 · Cited by 502

Bidirectional transcripts of the expanded C9orf72 hexanucleotide repeat are translated into aggregating dipeptide repeat proteins

Mori, K., Arzberger, T., Grässer, F. A., Gijselinck, I., May, S., Rentzsch, K., Weng, S., Schludi, M. H., van der Zee, J., Cruts, M., et al. (2013) · Acta Neuropathologica · doi:10.1007/s00401-013-1189-3 · Cited by 482

Nuclear-Import Receptors Reverse Aberrant Phase Transitions of RNA-Binding Proteins with Prion-like Domains

Guo, L. E., Kim, H. J., Wang, H. H., Monaghan, J., Freyermuth, F., Sung, J. C., O’Donovan, K., Fare, C. M., Diaz, Z., Singh, N., et al. (2018) · Cell · doi:10.1016/j.cell.2018.03.002 · Cited by 467

A single N‐terminal phosphomimic disrupts TDP‐43 polymerization, phase separation, and RNA splicing

Wang, A., Conicella, A. E., Schmidt, H. B., Martin, E. W., Rhoads, S. N., Reeb, A. N., Nourse, A., Montero, D. R., Ryan, V. H., Rohatgi, R., et al. (2018) · The EMBO Journal · doi:10.15252/embj.201797452 · Cited by 454

C9ORF72 repeat expansions in mice cause TDP-43 pathology, neuronal loss, and behavioral deficits

Chew, J., Gendron, T. F., Prudencio, M., Sasaguri, H., Zhang, Y., Castanedes‐Casey, M., Lee, C. W., Jansen‐West, K. R., Kurti, A., Murray, M. E., et al. (2015) · Science · doi:10.1126/science.aaa9344 · Cited by 426

Stress Granule Assembly Disrupts Nucleocytoplasmic Transport

Zhang, K., Daigle, J. G., Cunningham, K. M., Coyne, A. N., Ruan, K., Grima, J. C., Bowen, K., Wadhwa, H., Yang, P., Rigo, F., et al. (2018) · Cell · doi:10.1016/j.cell.2018.03.025 · Cited by 420

C9orf72 BAC Mouse Model with Motor Deficits and Neurodegenerative Features of ALS/FTD

Liu, Y., Pattamatta, A., Zu, T., Reid, T. S., Bardhi, O., Borchelt, D., Yachnis, A. T., & Ranum, L. P. W. (2016) · Neuron · doi:10.1016/j.neuron.2016.04.005 · Cited by 368

Dipeptide repeat protein pathology in C9ORF72 mutation cases: clinico-pathological correlations

Mackenzie, I. R., Arzberger, T., Kremmer, E., Troost, D., Lorenzl, S., Mori, K., Weng, S.-M., Haass, C., Kretzschmar, H. A., Edbauer, D., et al. (2013) · Acta Neuropathologica · doi:10.1007/s00401-013-1181-y · Cited by 345

Serum neurofilament light as a biomarker for mild traumatic brain injury in contact sports

Shahim, P., Zetterberg, H., Tegner, Y., & Blennow, K. (2017) · Neurology · doi:10.1212/wnl.0000000000003912 · Cited by 345

C9ORF72 poly(GA) aggregates sequester and impair HR23 and nucleocytoplasmic transport proteins

Zhang, Y., Gendron, T. F., Grima, J. C., Sasaguri, H., Jansen‐West, K. R., Xu, Y.-F., Katzman, R. B., Gass, J. M., Murray, M. E., Shinohara, M., et al. (2016) · Nature Neuroscience · doi:10.1038/nn.4272 · Cited by 324

C9orf72 frontotemporal lobar degeneration is characterised by frequent neuronal sense and antisense RNA foci

Mizielinska, S., Lashley, T., Norona, F. E., Clayton, E. L., Ridler, C. E., Fratta, P., & Isaacs, A. M. (2013) · Acta Neuropathologica · doi:10.1007/s00401-013-1200-z · Cited by 317

C 9orf72 ablation in mice does not cause motor neuron degeneration or motor deficits

Koppers, M., Blokhuis, A. M., Westeneng, H., Terpstra, M. L., Zundel, C. A. C., de Sá, R. V., Schellevis, R. D., Waite, A. J., Blake, D. J., Veldink, J. H., et al. (2015) · Annals of Neurology · doi:10.1002/ana.24453 · Cited by 301

Poly(GR) impairs protein translation and stress granule dynamics in C9orf72-associated frontotemporal dementia and amyotrophic lateral sclerosis

Zhang, Y., Gendron, T. F., Ebbert, M., O’Raw, A. D., Yue, M., Jansen‐West, K. R., Zhang, X., Prudencio, M., Chew, J., Cook, C. N., et al. (2018) · Nature Medicine · doi:10.1038/s41591-018-0071-1 · Cited by 299

Poly(GP) proteins are a useful pharmacodynamic marker for C9ORF72 -associated amyotrophic lateral sclerosis

Gendron, T. F., Chew, J., Stankowski, J. N., Hayes, L. R., Zhang, Y.-J., Prudencio, M., Carlomagno, Y., Daughrity, L. M., Jansen-West, K., Perkerson, E. A., et al. (2017) · Science Translational Medicine · doi:10.1126/scitranslmed.aai7866 · Cited by 265

Quantitative analysis and clinico-pathological correlations of different dipeptide repeat protein pathologies in C9ORF72 mutation carriers

Mackenzie, I. R. A., Frick, P., Grässer, F. A., Gendron, T. F., Petrucelli, L., Cashman, N. R., Edbauer, D., Kremmer, E., Prudlo, J., Troost, D., et al. (2015) · Acta Neuropathologica · doi:10.1007/s00401-015-1476-2 · Cited by 231

RAN translation at C9orf72-associated repeat expansions is selectively enhanced by the integrated stress response

Green, K. M., Glineburg, M. R., Kearse, M. G., Flores, B. N., Linsalata, A. E., Fedak, S., Goldstrohm, A. C., Barmada, S. J., & Todd, P. K. (2017) · Nature Communications · doi:10.1038/s41467-017-02200-0 · Cited by 221

Heterochromatin anomalies and double-stranded RNA accumulation underlie C9orf72 poly(PR) toxicity

Zhang, Y., Guo, L. E., Gonzales, P. K., Gendron, T. F., Wu, Y., Jansen‐West, K. R., O’Raw, A. D., Pickles, S. R., Prudencio, M., Carlomagno, Y., et al. (2019) · Science · doi:10.1126/science.aav2606 · Cited by 211

Nuclear import impairment causes cytoplasmic trans-activation response DNA-binding protein accumulation and is associated with frontotemporal lobar degeneration

Nishimura, A. L., Župunski, V., Troakes, C., Kathe, C., Fratta, P., Howell, M. T., Gallo, J., Hortobágyi, T., Shaw, C. E., & Rogelj, B. (2010) · Brain · doi:10.1093/brain/awq111 · Cited by 205

C9ORF72 GGGGCC repeat-associated non-AUG translation is upregulated by stress through eIF2α phosphorylation

Cheng, W., Wang, S., Mestre, A. A., Fu, C., Makarem, A. O., Xian, F., Hayes, L. R., Lopez-Gonzalez, R., Drenner, K., Jiang, J., et al. (2017) · Nature Communications · doi:10.1038/s41467-017-02495-z · Cited by 199

The dual functions of the extreme N-terminus of TDP-43 in regulating its biological activity and inclusion formation

Zhang, Y., Caulfield, T. R., Xu, Y., Gendron, T. F., Hubbard, J., Stetler, C. T., Sasaguri, H., Whitelaw, E. C., Cai, S., Lee, C. W., et al. (2013) · Human Molecular Genetics · doi:10.1093/hmg/ddt166 · Cited by 187

Sense-encoded poly-GR dipeptide repeat proteins correlate to neurodegeneration and uniquely co-localize with TDP-43 in dendrites of repeat-expanded C9orf72 amyotrophic lateral sclerosis

Saberi, S., Stauffer, J. E., Jiang, J., Díaz-García, S., Taylor, A. E., Schulte, D. J., Ohkubo, T., Schloffman, C. L., Maldonado, M., Baughn, M. W., et al. (2017) · Acta Neuropathologica · doi:10.1007/s00401-017-1793-8 · Cited by 187

Aberrant deposition of stress granule-resident proteins linked to C9orf72-associated TDP-43 proteinopathy

Chew, J., Cook, C. N., Gendron, T. F., Jansen‐West, K. R., del Rosso, G., Daughrity, L. M., Castanedes‐Casey, M., Kurti, A., Stankowski, J. N., Disney, M. D., et al. (2019) · Molecular Neurodegeneration · doi:10.1186/s13024-019-0310-z · Cited by 160

C9orf72 arginine-rich dipeptide repeat proteins disrupt karyopherin-mediated nuclear import

Hayes, L. R., Duan, L., Bowen, K., Kaláb, P., & Rothstein, J. D. (2020) · eLife · doi:10.7554/elife.51685 · Cited by 135

Cerebellar c9RAN proteins associate with clinical and neuropathological characteristics of C9ORF72 repeat expansion carriers

Gendron, T. F., van Blitterswijk, M., Bieniek, K. F., Daughrity, L. M., Jiang, J., Rush, B. K., Pedraza, O., Lucas, J. A., Murray, M. E., Desaro, P., et al. (2015) · Acta Neuropathologica · doi:10.1007/s00401-015-1474-4 · Cited by 106

Poly-GR dipeptide repeat polymers correlate with neurodegeneration and Clinicopathological subtypes in C9ORF72-related brain disease

Sakae, N., Bieniek, K. F., Zhang, Y., Ross, K., Gendron, T. F., Murray, M. E., Rademakers, R., Petrucelli, L., & Dickson, D. W. (2018) · Acta Neuropathologica Communications · doi:10.1186/s40478-018-0564-7 · Cited by 103

Misregulation of human sortilin splicing leads to the generation of a nonfunctional progranulin receptor

Prudencio, M., Jansen‐West, K. R., Lee, C. W., Gendron, T. F., Zhang, Y., Xu, Y.-F., Gass, J. M., Stuani, C., Stetler, C. T., Rademakers, R., et al. (2012) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1211577110 · Cited by 97

Dipeptide repeat protein inclusions are rare in the spinal cord and almost absent from motor neurons in C9ORF72 mutant amyotrophic lateral sclerosis and are unlikely to cause their degeneration

Gomez-Deza, J., Lee, Y.-B., Troakes, C., Nolan, M., Al-Sarraj, S., Gallo, J.-M., & Shaw, C. E. (2015) · Acta Neuropathologica Communications · doi:10.1186/s40478-015-0218-y · Cited by 93

Poly(GP), neurofilament and grey matter deficits in C9orf72 expansion carriers

Meeter, L. H. H., Gendron, T. F., Sias, A. C., Jiskoot, L. C., Russo, S. P., Donker Kaat, L., Papma, J. M., Panman, J. L., van der Ende, E. L., Dopper, E. G., et al. (2018) · Annals of Clinical and Translational Neurology · doi:10.1002/acn3.559 · Cited by 61

Amyotrophic lateral sclerosis

Feldman, E. L., Goutman, S. A., Petri, S., Mazzini, L., Savelieff, M. G., Shaw, P. J., & Sobue, G. (2022) · The Lancet · doi:10.1016/s0140-6736(22)01272-7 · Cited by 1,267

Emerging insights into the complex genetics and pathophysiology of amyotrophic lateral sclerosis

Goutman, S. A., Hardiman, O. M., Al‐Chalabi, A., Chiò, A., Savelieff, M. G., Kiernan, M. C., & Feldman, E. L. (2022) · The Lancet Neurology · doi:10.1016/s1474-4422(21)00414-2 · Cited by 432

Suppression of mutant C9orf72 expression by a potent mixed backbone antisense oligonucleotide

Tran, H., Moazami, M. P., Yang, H., McKenna-Yasek, D., Douthwright, C. L., Pinto, C., Metterville, J., Shin, M., Sanil, N., Dooley, C., et al. (2022) · Nature Medicine · doi:10.1038/s41591-021-01557-6 · Cited by 174

Intra-condensate demixing of TDP-43 inside stress granules generates pathological aggregates

Yan, X., Kuster, D., Mohanty, P., Nijssen, J., García, K. P., Morato, J. G., Rizuan, A., Franzmann, T. M., Sergeeva, A. V., Ly, A. M., et al. (2025) · Cell · doi:10.1016/j.cell.2025.04.039 · Cited by 182

Higher-order organization of biomolecular condensates

Fare, C. M., Villani, A., Drake, L. E., & Shorter, J. (2021) · Open Biology · doi:10.1098/rsob.210137 · Cited by 176

P4‐088: C9Orf72 Dipeptide Repeat Proteins Cause Intracellular Aggregation of Phosphorylated TDP‐43

Nonaka, T., & Hasegawa, M. (2016) · Alzheimer s & Dementia · doi:10.1016/j.jalz.2016.06.2177

C9ORF72 dipeptide repeat poly-GA inclusions promote intracellular aggregation of phosphorylated TDP-43

Nonaka, T., Masuda‐Suzukake, M., Hosokawa, M., Shimozawa, A., Hirai, S., Okado, H., & Hasegawa, M. (2018) · Human Molecular Genetics · doi:10.1093/hmg/ddy174 · Cited by 53

Modulating TDP-43 Protein Aggregation Directly and Indirectly in C. Elegans

Elshaalia, E. (2026) · Digital Commons - DU (University of Denver) · doi:10.56902/etdcrp.2026.150

C9ORF72 poly-GA inclusions promote phosphorylated TDP-43 aggregation in vitro and in vivo

Nonaka, T. (2018) · The Japanese Biochemical Society

Mitigation of TDP-43 toxic phenotype by an RGNEF fragment in amyotrophic lateral sclerosis models

Droppelmann, C. A., Campos‐Melo, D., Noches, V., McLellan, C., Szabla, R., Lyons, T. A., Amzil, H., Withers, B., Kaplanis, B., Sonkar, K. S., et al. (2024) · Brain · doi:10.1093/brain/awae078 · Cited by 15