Citations 5
Heterochromatin anomalies and double-stranded RNA accumulation underlie C9orf72 poly(PR) toxicity
Zhang, Yong‐Jie , Guo, Lin , Gonzales, Patrick , Gendron, Tania F. , Wu, Yanwei , Jansen‐West, Karen , O’Raw, Aliesha D. , Pickles, Sarah , Prudencio, Mercedes , Carlomagno, Yari , Gachechiladze, Mariam A. , Tian, Ruilin , Chew, Jeannie , DeTure, Michael , Lin, Wen-Lang, Tong, Jimei, Daughrity, Lillian M. , Yue, Mei, Song, Yuping , Andersen, Jonathan W. , Castanedes‐Casey, Monica , Kurti, Aishe, Antognetti, Giovanna, McCampbell, Alexander , Rademakers, Rosa , Oskarsson, Björn , Kampmann, Martin , Ward, Michael E. , Fryer, John Denis , Link, Christopher D. , Shorter, James , Petrucelli, Leonard , Gonzales, Patrick K , Pickles, Sarah R , Chew, Jeannie , DeTure, Michael , Daughrity, Lillian M , Castanedes-Casey, Monica , McCampbell, Alexander , Rademakers, Rosa , Oskarsson, Björn , Dickson, Dennis W , Kampmann, Martin , Ward, Michael E , Shorter, James , Petrucelli, Leonard , Zhang, Yong-Jie , Prudencio, Mercedes , O'Raw, Aliesha , Gendron, Tania F , Guo, Lin , Ludwig, Connor , Datta, Abhishek, Dickson, Dennis W.
Science | February 15, 2019 | Volume: 363 | Issue: 6428 | Pages: No page available
How dipeptide repeats cause pathology A repeat expansion in the chromosome 9 open reading frame 72 ( C9orf72 ) gene is the most common known cause of two neurodegenerative diseases: frontotemporal dementia and amyotrophic lateral sclerosis. This expansion leads to the abnormal production of proteins of repeating dipeptides, but their contribution to disease pathogenesis remains unclear. Zhang et al. engineered a mouse model to study the consequences of one of these dipeptides—prolinearginine dipeptide repeat protein, poly(PR)—in the brain. They found that poly(PR) caused neuron loss as well as motor and memory impairments. These detrimental effects resulted from poly(PR)-induced perturbation of heterochromatin function, a tightly packed form of DNA that represses gene expression. Science , this issue p. eaav2606
Abnormal expression of homeobox genes and transthyretin in C9ORF72 expansion carriers
Finch, NiCole A., Wang, Xue , Bieniek, Kevin F. , Wuu, Joanne , DeJesus‐Hernandez, Mariely, Brown, Patricia H., Chew, Jeannie , Jansen‐West, Karen , Daughrity, Lillian M. , Nicholson, Alexandra M., Murray, Melissa E. , Josephs, Keith A. , Parisi, Joseph E., Petersen, Ronald C. , Petrucelli, Leonard , Graff‐Radford, Neill R. , Asmann, Yan W. , Benatar, Michael , Bowser, Robert , Rademakers, Rosa , Blitterswijk, Marka van , Baker, Matthew C, Gendron, Tania F. , DeJesus-Hernandez, Mariely, Jansen-West, Karen R, Boylan, Kevin B, Baker, Matthew , Heckman, Michael G. , Knopman, David S. , Boeve, Bradley F. , Dickson, Dennis W. , Boylan, Khrista , van Blitterswijk, Marka , Murray, Melissa E
Neurology Genetics | June 8, 2017 | Volume: 3 | Issue: 4 | Pages: No page available
Poly(GP) proteins are a useful pharmacodynamic marker for C9ORF72 -associated amyotrophic lateral sclerosis
Chew, Jeannie , Stankowski, Jeannette N. , Hayes, Lindsey R. , Zhang, Yong‐Jie , Prudencio, Mercedes , Carlomagno, Yari , Daughrity, Lillian M. , Jansen‐West, Karen , Perkerson, Emilie A., O’Raw, Aliesha D. , Cook, Casey , Pregent, Luc , Belzil, Véronique , Blitterswijk, Marka van , Tabassian, Lilia J., Lee, Chris W. , Yue, Mei, Tong, Jimei, Song, Yuping , Castanedes‐Casey, Monica , Rousseau, Linda , Phillips, Virginia , Rademakers, Rosa , Fryer, John Denis , Rush, Beth , Pedraza, Otto , Caputo, Ana M., Desaro, Pamela , Palmucci, Carla, Robertson, A. , Diehl, Nancy N. , Wiggs, Edythe, Tierney, Michael , Braun, Laura, Farren, Jennifer, Lacomis, David , Fournier, Christina , McCluskey, Leo, Elman, Lauren , Toledo, Jon B. , McBride, Jennifer D. , Tiloca, Cinzia , Morelli, Claudia , Poletti, Barbara , Solca, Federica , Wuu, Joanne , Jockel‐Balsarotti, Jennifer , Rigo, Frank , Ambrose, Christine, Yang, Weixing , Raitcheva, Denitza , Antognetti, Giovanna, McCampbell, Alexander , Boxer, Adam L. , Brown, Robert H. , Bowser, Robert , Miller, Timothy M. , Trojanowski, John Q. , Hu, William T. , Ratti, Antonia , Benatar, Michael , Glass, Jonathan D. , Floeter, Mary Kay, Petrucelli, Leonard , Gendron, Tania F. , Zhang, Yong-Jie , Prudencio, Mercedes , Carlomagno, Yari , Jansen-West, Karen, O'Raw, Aliesha , Pregent, Luc , Belzil, Veronique , van Blitterswijk, Marka , Castanedes-Casey, Monica , Rousseau, Linda , Phillips, Virginia , Rademakers, Rosa , Fryer, John D., Desaro, Pamela , Palmucci, Carla , Robertson, Amelia , Lacomis, David , Ladha, Shafeeq , Tiloca, Cinzia , Poletti, Barbara , Solca, Federica , Prelle, Alessandro , Jockel-Balsarotti, Jennifer , Yang, Weixing , Raitcheva, Denitza , Benatar, Michael , Silani, Vincenzo , Boylan, Kevin B, Petrucelli, Leonard , Dickson, Dennis W. , Heckman, Michael G. , Ladha, Shafeeq , Datta, Abhishek , Swieten, John C. van , Miller, Bruce L. , Grossman, Murray , Berry, James D. , Traynor, Bryan J. , Disney, Matthew D. , Silani, Vincenzo , Rothstein, Jeffrey D. , Boylan, Khrista , Hu, William T.
Science Translational Medicine | March 29, 2017 | Volume: 9 | Issue: 383 | Pages: No page available
Poly(GP) proteins are a promising pharmacodynamic marker for developing and testing therapeutics for treating C9ORF72 -associated amyotrophic lateral sclerosis.
Spt4 selectively regulates the expression of C9orf72 sense and antisense mutant transcripts
Kramer, Nicholas J. , Carlomagno, Yari , Zhang, Yong‐Jie , Almeida, Sandra , Cook, Casey , Prudencio, Mercedes , Blitterswijk, Marka van , Belzil, Véronique , Couthouis, Julien , Paul, Joseph W. , Goodman, Lindsey D. , Daughrity, Lillian M. , Chew, Jeannie , Garrett, Aliesha, Pregent, Luc , Jansen‐West, Karen , Tabassian, Lilia J., Rademakers, Rosa , Graff‐Radford, Neill R. , Josephs, Keith A. , Parisi, Joseph E., Petersen, Ronald C. , Deng, Ning , Feng, Yanan , Cheng, Tzu-Hao, Cohen, Stanley N. , Link, Christopher D. , Gao, Fen‐Biao , Petrucelli, Leonard , Gitler, Aaron D. , O’Raw, Aliesha D. , Cook, Casey N, Gendron, Tania F. , van Blitterswijk, Marka, Daughrity, Lillian, Jansen-West, Karen, Boylan, Kevin, Boylan, Khrista , Knopman, David S. , Boeve, Bradley F. , Dickson, Dennis W. , Bonini, Nancy M. , Zhang, Yong-Jie , Prudencio, Mercedes , O'Raw, Aliesha , van Blitterswijk, Marka , Gitler, Aaron D
Science | August 11, 2016 | Volume: 353 | Issue: 6300 | Pages: 708-712
Targeting three defects with one strategy The neurodegenerative diseases amyotrophic lateral sclerosis and frontotemporal dementia are most commonly caused by a mutation in the C9orf72 gene. The mutation is an expanded hexanucleotide repeat in a noncoding region. The expanded repeat produces sense and antisense RNA transcripts, which accumulate in patient cells and appear to sequester RNA-binding proteins. The sense and antisense transcripts are also translated into dipeptide repeat proteins, which are aggregation-prone and accumulate in the brain and spinal cord. Last, loss of function from reduced expression of C9orf72 in neurons and glia could contribute to the disease. Kramer et al. targeted both sense and antisense repeats by blocking a single gene called SPT4 , which mitigated degeneration in human cells by reducing all three types of pathologies. Science , this issue p. 708
C9ORF72 repeat expansions in mice cause TDP-43 pathology, neuronal loss, and behavioral deficits
Chew, Jeannie , Prudencio, Mercedes , Sasaguri, Hiroki , Zhang, Yong‐Jie , Castanedes‐Casey, Monica , Lee, Chris W. , Jansen‐West, Karen , Kurti, Aishe, Murray, Melissa E. , Bieniek, Kevin F. , Bauer, Peter , Whitelaw, Ena C., Rousseau, Linda , Stankowski, Jeannette N. , Stetler, Caroline, Daughrity, Lillian M. , Perkerson, Emilie A., Desaro, Pamela , Johnston, Amelia, Overstreet, Karen, Edbauer, Dieter , Rademakers, Rosa , Fryer, John Denis , Petrucelli, Leonard , Gendron, Tania F. , Castanedes-Casey, Monica, Jansen-West, Karen, Bauer, Peter O, Boylan, Kevin B, Fryer, John D., Boylan, Khrista , Dickson, Dennis W. , Zhang, Yong-Jie , Prudencio, Mercedes , Murray, Melissa E
Science | May 14, 2015 | Volume: 348 | Issue: 6239 | Pages: 1151-1154
A mouse model for ALS A G4C2 repeat expansion in C9ORF72 is known to be the major genetic cause of frontotemporal dementia and amyotrophic lateral sclerosis (c9FTD/ALS). However, a lack of animal models recapitulating key disease features has hindered efforts to understand and prevent c9FTD/ALS-related neurodegeneration. Until now. Chew et al. describe a mouse model that mimics both neuropathological and clinical phenotypes of c9FTD/ALS. Science , this issue p. 1151