Citations 3
Poly(ADP-ribose) promotes toxicity of C9ORF72 arginine-rich dipeptide repeat proteins
Gao, Junli , Mewborne, Quinlan T. , Girdhar, Amandeep , Sheth, Udit , Coyne, Alyssa N. , Punathil, Ritika , Kang, Bong Gu , Dasovich, Morgan , Veire, Austin M. , Hernandez, Mariely DeJesus, Liu, Shuaichen , Shi, Zheng , Dafinca, Ruxandra , Talbot, Kevin , Zhang, Yong‐Jie , Petrucelli, Leonard , Blitterswijk, Marka van , Guo, Lin , Dawson, Ted M. , Veire, Austin , DeJesus Hernandez, Mariely, Fouquerel, Elise , Talbot, Kevin , Kam, Tae-In , Zhang, Yong-Jie , Dickson, Dennis W , Petrucelli, Leonard , van Blitterswijk, Marka , Guo, Lin , Dawson, Ted M , Dawson, Valina L , Leung, Anthony K L , Lloyd, Thomas E , Gendron, Tania F , Rothstein, Jeffrey D , Zhang, Ke , Coyne, Alyssa N , Sheth, Udit , Liu, Shuaichen, Kam, Tae‐In , Dickson, Dennis W. , Dawson, Valina L. , Gendron, Tania F. , Rothstein, Jeffrey D. , Zhang, Ke
Science Translational Medicine | September 14, 2022 | Volume: 14 | Issue: 662 | Pages: No page available
Arginine-rich dipeptide repeat proteins (R-DPRs), abnormal translational products of a GGGGCC hexanucleotide repeat expansion in C9ORF72 , play a critical role in C9ORF72 -related amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD), the most common genetic form of the disorders (c9ALS/FTD). R-DPRs form liquid condensates in vitro, induce stress granule formation in cultured cells, aggregate, and sometimes coaggregate with TDP-43 in postmortem tissue from patients with c9ALS/FTD. However, how these processes are regulated is unclear. Here, we show that loss of poly(ADP-ribose) (PAR) suppresses neurodegeneration in c9ALS/FTD fly models and neurons differentiated from patient-derived induced pluripotent stem cells. Mechanistically, PAR induces R-DPR condensation and promotes R-DPR–induced stress granule formation and TDP-43 aggregation. Moreover, PAR associates with insoluble R-DPR and TDP-43 in postmortem tissue from patients. These findings identified PAR as a promoter of R-DPR toxicity and thus a potential target for treating c9ALS/FTD.
Association of Variants in the SPTLC1 Gene With Juvenile Amyotrophic Lateral Sclerosis
Johnson, Janel O., Chia, Ruth , Miller, Danny E. , Kumaran, Ravindran, Abramzon, Yevgeniya, Alahmady, Nada F. , Topp, Simon , Gibbs, J. Raphael , Cookson, Mark , Sabir, Marya S. , Dalgard, Clifton L. , Troakes, Claire , Jones, Ashley R., Shatunov, Aleksey , Iacoangeli, Alfredo , Khleifat, Ahmad Al , Ticozzi, Nicola , Gellera, Cinzia , Blair, Ian P. , Dobson‐Stone, Carol , Bonkowski, Emily , Palvadeau, Robin , Tienari, Pentti J. , Morrison, Karen , Shaw, Pamela J. , Brown, Robert H., Calvo, Andrea, Al-Saif, Hind, Leigh, Fawn, Chang, Irene J. , Perlman, Seth J. , Scott, Anna I. , Başak, A. Nazlı , Landers, John E. , Crawford, Thomas O. , Smith, Bradley , Traynor, Bryan J. , Gkazi, Athina Soragia, Kenna, Kevin P., Keagle, Pamela, Tiloca, Cinzia , Vance, Caroline , King, Andrew , Pensato, Viviana , Castellotti, Barbara , Baas, Frank , Asbroek, Anneloor L.M.A. ten , McKenna‐Yasek, Diane, McLaughlin, Russell L. , Polak, Meraida , Asress, Seneshaw, Stević, Zorica, D’Alfonso, Sandra , Mazzini, Letizia, Bo, Roberto Del, Gagliardi, Stella , Querin, Giorgia, Bertolin, Cinzia , Rademakers, Rosa, Blitterswijk, Marka van , Lauria, Giuseppe, Corrado, Lucia , Sorarú, Gianni , Williams, Kelly L. , Leblond-Manry, Claire, Hardiman, Orla , Berg, Leonard H. van den, Pall, Hardev, Taroni, Franco , Wu, Zheyang , Glass, Jonathan D., Ratti, Antonia, Adeleye, Adelani, Alba, Camille , Viollet, Coralie , Bačíková, Dagmar, Hupalo, Daniel N., Pollard, Harvey B. , Martinez, Elisa McGrath, Ahmed, Sarah , Arepalli, Sampath, Baloh, Robert H. , Bowser, Robert , Campbell, Roy H. , Camu, William, Cooper‐Knock, Johnathan , Ding, Jinhui, Drory, Vivian E., Dunckley, Travis , Eicher, John D., England, Bryce, Faghri, Faraz , Feldman, Eva, Floeter, Mary Kay, Fratta, Pietro , Geiger, Joshua T. , Gibson, Summer, Hardy, John , Harms, Matthew , Heiman‐Patterson, Terry , Hernandez, Dena G., Jansson, Lilja, Kowall, Neil W. , Laaksovirta, Hannu , Landi, Francesco , Ber, Isabelle Le , Lumbroso, Serge , MacGowan, Daniel J., Maragakis, Nicholas J., Mouzat, Kévin , Murphy, Natalie A., Myllykangas, Liisa , Nalls, Mike A., Orrell, Richard W., Ostrow, Lyle W., Pickering‐Brown, Stuart , Pioro, Erik P., Pletniková, Olga , Ravits, John , Rivera, Alberto , Robberecht, Wim, Rogaeva, Ekaterina, Rollinson, Sara, Rothstein, Jeffrey D., Scholz, Sonja W. , Sendtner, Michael , Sidle, Katie, Singleton, Andrew, Smith, Nathan, Stone, David J. , Troncoso, Juan C., Valori, Miko , Damme, Philip Van , Deerlin, Vivianna M Van, Bosch, Ludo Van Den , Zinman, Lorne, Landers, John E., Chiò, Adriano, Angelocola, Stefania, Ausiello, Francesco P., Barberis, Marco, Bartolomei, Ilaria, Battistini, Stefania, Bisogni, Giulia , Borghero, Giuseppe , Brunetti, Maura, Canale, Fabrizio , Canosa, Antonio, Cantisani, Teresa A., Cardinali, Patrizio, Casale, Federico , Colletti, Tiziana , Conforti, F. L. , Conte, Amelia , Conti, Elisa, Corbo, Massimo , Cuccu, Stefania, D’Errico, Eustachio , Marco, Giovanni De , Dubbioso, Raffaele, Ferrarese, Carlo , Ferraro, Pilar M. , Floris, Gianluca , Fuda, Giuseppe, Gallone, Salvatore , Gianferrari, Giulia , Giannini, Fabio, Grassano, Maurizio, Greco, Lucia Catherine , Iazzolino, Barbara, Introna, Alessandro , Logroscino, Giancarlo , Logullo, Francesco, Lunetta, Christian , Mandich, Paola , Mandrioli, Jessica , Manera, Umberto , Manganelli, Fiore, Martinelli, Ilaria , Moglia, Cristina, Mosca, Lorena, Murru, Maria Rita, Origone, Paola , Petrelli, Cristina, Pozzi, Susanna, Pugliatti, Maura , Ricci, Claudia , Riolo, Giulia , Russo, Massimo, Salamone, Paolina, Salivetto, Marco, Salvi, Fabrizio, Santarelli, Marialuisa, Sbaiz, Luca, Sideri, Riccardo , Simonini, Cecilia , Tanel, Raffaella , Tedeschi, Gioacchino, Ticca, Anna, Torriello, Antonella, Tranquilli, Stefania, Tremolizzo, Lucio , Vasta, Rosario , Vacchiano, Veria, Volanti, Paolo , Zollino, Marcella , Lauria, Giuseppe , Ratti, Antonia , Ostrow, Lyle W. , Fratta, Pietro , Chia, Ruth , Logroscino, Giancarlo , van Blitterswijk, Marka , Scholz, Sonja W , Van Den Bosch, Ludo , Van Damme, Philip , Hardy, John , Fratta, Pietro , Fratta, Pietro , Troakes, Claire , Hardiman, Orla , Dalgard, Clifton L , Myllykangas, Liisa , Li, Rachel , Renton, Alan , Jones, Ashley R., Silani, Vincenzo , Kwok, John B. , Al‐Chalabi, Ammar , Calvo, Andrea , Mora, Gabriele , Gotkine, Marc , Glass, Ian A. , Shaw, Christopher E. , Chiò, Adriano , Fallini, Claudia , Gkazi, Soragia Athina , Scotter, Emma L. , Kenna, Kevin Patrick , Keagle, Pamela , Colombrita, Claudia , Asress, Seneshaw, Esteban‐Pérez, Jesús , Mazzini, Letizia , Comi, Giacomo P. , Ceroni, Mauro , Rheenen, Wouter van , Rademakers, Rosa , Duga, Stefano , Corti, Stefania Paola , Cereda, Cristina , Nicholson, Garth A. , Rouleau, Guy Armand , Veldink, Jan H. , Berg, Leonard H. van den , Turner, Martin R. , Talbot, Kevin , García‐Redondo, Alberto , Adeleye, Adelani, Soltis, Anthony R. , Sukumar, Gauthaman , Wilkerson, Matthew D. , Brady, Christopher B. , Brice, Alexis , Broach, James R , Campbell, Roy H., Ding, Jinhui , Drepper, Carsten , Gerhard, Glenn S. , Harms, Matthew B. , Hernandez, Dena G., Kirby, Janine , Landeck, Natalie , Maragakis, Nicholas J. , Pamphlett, Roger , Pliner, Hannah A. , Pulst, Stefan M. , Rothstein, Jeffrey D. , Simmons, Zachary , Singleton, Andrew , Smith, Nathan, Troncoso, Juan C. , Deerlin, Vivianna M. Van , Zinman, Lorne , Ausiello, Francesco Pio, Barberis, Marco , Battistini, Stefania , Bersano, Enrica , Brunetti, Maura , Cabona, Corrado , Canosa, Antonio , Capasso, Margherita , Caponnetto, Claudia , Carrera, Paola , Bella, Eleonora Dalla , Dubbioso, Raffaele , Filippi, Massimo , Fini, Nicola , Grassano, Maurizio , Iazzolino, Barbara, Bella, Vincenzo La , Lattante, Serena , Liguori, Rocco , Manganelli, Fiore , Marangi, Giuseppe , Marinou, Kalliopi , Marrosu, Maria Giovanna , Messina, Sonia , Moglia, Cristina , Mosca, Lorena, Passaniti, Carla , Petrucci, Antonio , Quattrini, Angelo , Riva, Nilo , Russo, Massimo, Sabatelli, Mario , Salamone, Paolina , Simone, Isabella Laura , Spataro, Rossella , Tedeschi, Gioacchino , Trojsi, Francesca , Vacchiano, Veria , Vita, Giuseppe , Zucchi, Elisabetta
JAMA Neurology | August 30, 2021 | Volume: 78 | Issue: 10 | Pages: 1236
A blinded international study on the reliability of genetic testing for GGGGCC-repeat expansions in C9orf72 reveals marked differences in results among 14 laboratories
Akimoto, Chizuru, Volk, Alexander E. , Blitterswijk, Marka van , Broeck, Marleen Van den , Leblond, Claire S. , Lumbroso, Serge , Camu, William, Neitzel, Birgit, Onodera, Osamu , Pinto, Susana , Weber, Markus , Smith, Bradley , Proven, Melanie , Talbot, Kevin , Keagle, Pamela , Chesi, Alessandra , Ratti, Antonia , Zee, Julie van der , Alstermark, Helena, Birve, Anna, Calini, Daniela, Nordin, Angelica , Tradowsky, Daniela C, Just, Walter, Daoud, Hussein , Angerbauer, Sabrina, DeJesus‐Hernandez, Mariely, Konno, Takuya , Lloyd-Jani, Anjali, Mouzat, Kévin , Landers, John E. , Veldink, Jan H. , Silani, Vincenzo , Gitler, Aaron D. , Shaw, Christopher E. , Berg, Leonard H. van den , Broeckhoven, Christine Van , Rademakers, Rosa , Kubisch, Christian , van Blitterswijk, Marka, DeJesus-Hernandez, Mariely, Rheenen, Wouter van , Tradowsky, Daniela C., Carvalho, Mamede A. de , Rouleau, Guy Armand , Andersen, Peter Munch , van Blitterswijk, Marka , Silani, Vincenzo , Gitler, Aaron D , Veldink, Jan H , Konno, Takuya , Onodera, Osamu , Talbot, Kevin , Volk, Alexander E
Journal of Medical Genetics | April 5, 2014 | Volume: 51 | Issue: 6 | Pages: 419-424
Background The GGGGCC-repeat expansion in C9orf72 is the most frequent mutation found in patients with amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Most of the studies on C9orf72 have relied on repeat-primed PCR (RP-PCR) methods for detection of the expansions. To investigate the inherent limitations of this technique, we compared methods and results of 14 laboratories. Methods The 14 laboratories genotyped DNA from 78 individuals (diagnosed with ALS or FTD) in a blinded fashion. Eleven laboratories used a combination of amplicon-length analysis and RP-PCR, whereas three laboratories used RP-PCR alone; Southern blotting techniques were used as a reference. Results Using PCR-based techniques, 5 of the 14 laboratories got results in full accordance with the Southern blotting results. Only 50 of the 78 DNA samples got the same genotype result in all 14 laboratories. There was a high degree of false positive and false negative results, and at least one sample could not be genotyped at all in 9 of the 14 laboratories. The mean sensitivity of a combination of amplicon-length analysis and RP-PCR was 95.0% (73.9–100%), and the mean specificity was 98.0% (87.5–100%). Overall, a sensitivity and specificity of more than 95% was observed in only seven laboratories. Conclusions Because of the wide range seen in genotyping results, we recommend using a combination of amplicon-length analysis and RP-PCR as a minimum in a research setting. We propose that Southern blotting techniques should be the gold standard, and be made obligatory in a clinical diagnostic setting.