C9orf72 Proteins Regulate Autophagy and Undergo Autophagosomal or Proteasomal Degradation in a Cell Type-Dependent Manner by Stina Leskelä, Nadine Huber, Hannah Rostalski, Teemu Natunen, Anne M. Remes, Mari Takalo, Mikko Hiltunen, Annakaisa Haapasalo

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An integrated multi-omic analysis of iPSC-derived motor neurons from C9ORF72 ALS patients by Fraenkel, Ernest

“…We used a C9ORF72 Drosophila model to distinguish pathways contributing to disease phenotypes from compensatory ones and confirmed alterations in some pathways in postmortem spinal cord tissue of patients with ALS. …”
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C9orf72 and RAB7L1 regulate vesicle trafficking in amyotrophic lateral sclerosis and frontotemporal dementia by Aoki, Y, Manzano, R, Lee, Y, Dafinca, R, Aoki, M, Douglas, A, Varela, M, Sathyaprakash, C, Scaber, J, Barbagallo, P, Vader, P, Mäger, I, Ezzat, K, Turner, M, Ito, N, Gasco, S, Ohbayashi, N, El Andaloussi, S, Takeda, S, Fukuda, M, Talbot, K, Wood, M

“…A non-coding hexanucleotide repeat expansion in intron 1 of the C9orf72 gene is the most common cause of amyotrophic lateral sclerosis and frontotemporal dementia (C9ALS/FTD), however, the precise molecular mechanism by which the C9orf72 hexanucleotide repeat expansion directs C9ALS/FTD pathogenesis remains unclear. …”

C9ORF72 and RAB7L1 regulate vesicle trafficking in amyotrophic lateral sclerosis and frontotemporal dementia by Manzano, R, Aoki, Y, Lee, Y, Nca, RD, Aoki, M, Douglas, AGL, Varela, MA, Sathyaprakash, C, Scaber, J, Barbagallo, P, Vader, P, Mager, I, Ezzat, K, Turner, MR, Ito, N, Gasco, S, Ohbayashi, N, El Andaloussi, S, Taked, S, Fukuda, M, Talbot, K, Wood, MJA

Genetic alterations of C9orf72, SOD1, TARDBP, FUS, and UBQLN2 genes in patients with Amyotrophic Lateral Sclerosis by Ciftci Vildan, Darbas Sule, Bilgen Turker, Uysal Hilmi, Karauzum Berker Sibel

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Poly‐GP in cerebrospinal fluid links C9orf72‐associated dipeptide repeat expression to the asymptomatic phase of ALS/FTD by Carina Lehmer, Patrick Oeckl, Jochen H Weishaupt, Alexander E Volk, Janine Diehl‐Schmid, Matthias L Schroeter, Martin Lauer, Johannes Kornhuber, Johannes Levin, Klaus Fassbender, Bernhard Landwehrmeyer, German Consortium for Frontotemporal Lobar Degeneration, Martin H Schludi, Thomas Arzberger, Elisabeth Kremmer, Andrew Flatley, Regina Feederle, Petra Steinacker, Patrick Weydt, Albert C Ludolph, Dieter Edbauer, Markus Otto

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Differential toxicity and localization of arginine-rich C9ORF72 dipeptide repeat proteins depend on de-clustering of positive charges by Tamami Miyagi, Koji Ueda, Masahiro Sugimoto, Takuya Yagi, Daisuke Ito, Rio Yamazaki, Satoshi Narumi, Yuhei Hayamizu, Hiroshi Uji-i, Masahiko Kuroda, Kohsuke Kanekura

“…Summary: Arginine-rich dipeptide repeat proteins (R-DPRs), poly(PR) and poly(GR), translated from the hexanucleotide repeat expansion in the amyotrophic lateral sclerosis (ALS)-causative C9ORF72 gene, contribute significantly to pathogenesis of ALS. …”
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The ALS/FTD-related C9orf72 hexanucleotide repeat expansion forms RNA condensates through multimolecular G-quadruplexes by Federica Raguseo, Yiran Wang, Jessica Li, Marija Petrić Howe, Rubika Balendra, Anouk Huyghebaert, Devkee M. Vadukul, Diana A. Tanase, Thomas E. Maher, Layla Malouf, Roger Rubio-Sánchez, Francesco A. Aprile, Yuval Elani, Rickie Patani, Lorenzo Di Michele, Marco Di Antonio

“…The most common genetic cause of ALS/FTD is expansion of the intronic hexanucleotide repeat (GGGGCC) n in C9orf72. Here, we investigate the formation of nucleic acid secondary structures in these expansion repeats, and their role in generating condensates characteristic of ALS/FTD. …”
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Dipeptide Repeat Pathology in <i>C9orf72</i>-ALS Is Associated with Redox, Mitochondrial and NRF2 Pathway Imbalance by José Jiménez-Villegas, Janine Kirby, Ana Mata, Susana Cadenas, Martin R. Turner, Andrea Malaspina, Pamela J. Shaw, Antonio Cuadrado, Ana I. Rojo

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Synaptic proteomics reveal distinct molecular signatures of cognitive change and C9ORF72 repeat expansion in the human ALS cortex by Zsofia I. Laszlo, Nicole Hindley, Anna Sanchez Avila, Rachel A. Kline, Samantha L. Eaton, Douglas J. Lamont, Colin Smith, Tara L. Spires-Jones, Thomas M. Wishart, Christopher M. Henstridge

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Two Families with SOD1 (L144F) and C9orf72 Gene Mutations and an Overview of Amyotrophic Lateral Sclerosis by Nazlı Gamze Bülbül, Yaprak Seçil, Nazlı Başak, Yeşim Beckmann, Hatice Sabiha Türe, Ceren Tunca, Aslıhan Özoğuz

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Altered Blood–Brain Barrier Dynamics in the C9orf72 Hexanucleotide Repeat Expansion Mouse Model of Amyotrophic Lateral Sclerosis by Yijun Pan, Yoshiteru Kagawa, Jiaqi Sun, Bradley J. Turner, Cheng Huang, Anup D. Shah, Ralf B. Schittenhelm, Joseph A. Nicolazzo

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<em>C9orf72</em> Intermediate Repeats Confer Genetic Risk for Severe COVID-19 Pneumonia Independently of Age by Isabella Zanella, Eliana Zacchi, Simone Piva, Massimiliano Filosto, Giada Beligni, Diana Alaverdian, Sara Amitrano, Francesca Fava, Margherita Baldassarri, Elisa Frullanti, Ilaria Meloni, Alessandra Renieri, GEN-COVID Multicenter Study, GEVACOBA Study Group, Francesco Castelli, Eugenia Quiros-Roldan

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Metformin ameliorates the mitochondrial damage induced by C9ORF72 amyotrophic lateral sclerosis/frontotemporal dementia-related poly-GR by FENG Yiyuan, XU Zhongyun, YIN Yafu, WANG Hui, CHENG Weiwei

Subjects: “…c9orf72 amyotrophic lateral sclerosis/ frontotemporal dementia (c9orf72 als/ftd)…”
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Pathologic expansion in the C9orf72 gene is associated with accelerated decline of respiratory function and decreased survival in amyotrophic lateral sclerosis by Gabriel Miltenberger-Miltenyi, Vasco A. Conceição, Marta Gromicho, Ana Catarina Pronto-Laborinho, Susana Pinto, Mamede de Carvalho

“…AbstractIntroduction Respiratory insufficiency is the main cause of death in amyotrophic lateral sclerosis (ALS). As the C9orf72 repeat expansion represents the most common genetic risk factor for this disease, we studied whether C9orf72 modulates respiratory function and survival.Methods Demographic and clinical data, and C9orf72 status were collected from 372 ALS patients followed in our centre. …”
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Human C9ORF72 Hexanucleotide Expansion Reproduces RNA Foci and Dipeptide Repeat Proteins but Not Neurodegeneration in BAC Transgenic Mice by Peters, Owen M., Cabrera, Gabriela Toro, Tran, Helene, Gendron, Tania F., McKeon, Jeanne E., Metterville, Jake, Weiss, Alexandra, Wightman, Nicholas, Salameh, Johnny, Kim, Juhyun, Sun, Huaming, Boylan, Kevin B., Dickson, Dennis, Kennedy, Zachary, Lin, Ziqiang, Zhang, Yong-Jie, Daughrity, Lillian, Jung, Chris, Gao, Fen-Biao, Bosco, Daryl A., Brown, Solange P., de Jong, Pieter, Petrucelli, Leonard, Mueller, Christian, Brown, Robert H., Horvitz, Howard Robert, Sapp, Peter C.

“…To investigate the pathological role of C9ORF72 in these diseases, we generated a line of mice carrying a bacterial artificial chromosome containing exons 1 to 6 of the human C9ORF72 gene with approximately 500 repeats of the GGGGCC motif. …”
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Dissecting the contribution of dipeptide repeats to the toxicity in C9orf72 iPSC-derived neurons from ALS/FTD patients by Barbagallo, P

“…<p>A large (GGGGCC) repeat expansion in C9ORF72 gene is the commonest genetic cause of amyotrophic lateral sclerosis (ALS). …”

Beyond C9orf72: repeat expansions and copy number variations as risk factors of amyotrophic lateral sclerosis across various populations by Zsófia Flóra Nagy, Margit Pál, József I. Engelhardt, Mária Judit Molnár, Péter Klivényi, Márta Széll

“…The most frequent genetic cause of ALS is the repeat expansion of the C9orf72 gene. With the emergence of next-generation sequencing techniques and copy number alteration calling tools the focus in ALS genetics has shifted from disease causing genes and mutations towards genetic susceptibility and risk factors. …”
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Loss of C9orf72 perturbs the Ran-GTPase gradient and nucleocytoplasmic transport, generating compositionally diverse Importin β-1 granules by Philip McGoldrick, Agnes Lau, Zhipeng You, Thomas M. Durcan, Janice Robertson

“…Summary: A hexanucleotide (GGGGCC)n repeat expansion in C9orf72 causes amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD), eliciting toxic effects through generation of RNA foci, dipeptide repeat proteins, and/or loss of C9orf72 protein. …”
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Differences in Cerebral Glucose Metabolism in ALS Patients with and without <i>C9orf72</i> and <i>SOD1</i> Mutations by Joke De Vocht, Donatienne Van Weehaeghe, Fouke Ombelet, Pegah Masrori, Nikita Lamaire, Martijn Devrome, Hilde Van Esch, Mathieu Moisse, Michel Koole, Patrick Dupont, Koen Van Laere, Philip Van Damme

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