C9orf72-mediated neurodegeneration: mechanisms and therapeutics

Project Information

C9ND

Grant agreement ID: 648716

DOI

10.3030/648716

Project closed

EC signature date 29 May 2015

Start date 1 October 2015

End date 31 March 2021

Funded under

• EXCELLENT SCIENCE - European Research Council (ERC)

Total cost

€ 1 985 699,00

EU contribution

€ 1 985 699,00

Coordinated by

UNIVERSITY COLLEGE LONDON
United Kingdom

CORDIS provides links to public deliverables and publications of HORIZON projects.

Links to deliverables and publications from FP7 projects, as well as links to some specific result types such as dataset and software, are dynamically retrieved from OpenAIRE .

Publications

Peer reviewed articles (20)

Enhanced insulin signalling ameliorates C9orf72 hexanucleotide repeat expansion toxicity in Drosophila

Author(s): Magda L Atilano, Sebastian Grönke, Teresa Niccoli, Liam Kempthorne, Oliver Hahn, Javier Morón-Oset, Oliver Hendrich, Miranda Dyson, Mirjam Lisette Adams, Alexander Hull, Marie-Therese Salcher-Konrad, Amy Monaghan, Magda Bictash, Idoia Glaria, Adrian M Isaacs, Linda Partridge
Published in: eLife, Issue 10, 2021, ISSN 2050-084X
Publisher: eLife Sciences Publications
DOI: 10.7554/elife.58565

FUS ALS-causative mutations impair FUS autoregulation and splicing factor networks through intron retention.

Author(s): Agnieszka M Ule; Jack Humphrey; Irene Bozzoni; Irene Bozzoni; Carmelo Milioto; Vincent Plagnol; Maria Giovanna Garone; David Robaldo; Cristian Bodo; Seth Jarvis; Gianni Sorarù; Martha McLaughlin; Nicol Birsa; Marc-David Ruepp; Alessandro Rosa; Alessandro Rosa; Anna-Leigh Brown; Andrea B. Eberle; Anny Devoy; Anny Devoy; Adrian M. Isaacs; Matthew Bentham; Elizabeth M. C. Fisher; Giampietro Schiavo;
Published in: Nucleic Acids Research, Issue 2, 2020, ISSN 1362-4962
Publisher: Oxford University Press
DOI: 10.7892/boris.144156

Soluble and insoluble dipeptide repeat protein measurements in C9orf72-frontotemporal dementia brains show regional differential solubility and correlation of poly-GR with clinical severity

Author(s): Annelies Quaegebeur, Idoia Glaria, Tammaryn Lashley, Adrian M. Isaacs
Published in: Acta Neuropathologica Communications, Issue 8/1, 2020, ISSN 2051-5960
Publisher: BioMed Central
DOI: 10.1186/s40478-020-01036-y

Sense and antisense RNA are not toxic in Drosophila models of C9orf72-associated ALS/FTD

Author(s): Thomas G. Moens, Sarah Mizielinska, Teresa Niccoli, Jamie S. Mitchell, Annora Thoeng, Charlotte E. Ridler, Sebastian Grönke, Jacqueline Esser, Amanda Heslegrave, Henrik Zetterberg, Linda Partridge, Adrian M. Isaacs
Published in: Acta Neuropathologica, Issue 135/3, 2018, Page(s) 445-457, ISSN 0001-6322
Publisher: Springer Verlag
DOI: 10.1007/s00401-017-1798-3

Ageing as a risk factor for ALS/FTD

Author(s): Teresa Niccoli, Linda Partridge, Adrian M. Isaacs
Published in: Human Molecular Genetics, Issue 26/R2, 2017, Page(s) R105-R113, ISSN 0964-6906
Publisher: Oxford University Press
DOI: 10.1093/hmg/ddx247

Bidirectional nucleolar dysfunction in C9orf72 frontotemporal lobar degeneration

Author(s): Sarah Mizielinska, Charlotte E. Ridler, Rubika Balendra, Annora Thoeng, Nathan S. Woodling, Friedrich A. Grässer, Vincent Plagnol, Tammaryn Lashley, Linda Partridge, Adrian M. Isaacs
Published in: Acta Neuropathologica Communications, Issue 5/1, 2017, ISSN 2051-5960
Publisher: BioMed Central
DOI: 10.1186/s40478-017-0432-x

G‐quadruplex‐binding small molecules ameliorate C9orf72 FTD/ALS pathology in vitro and in vivo

Author(s): Roberto Simone, Rubika Balendra, Thomas G Moens, Elisavet Preza, Katherine M Wilson, Amanda Heslegrave, Nathan S Woodling, Teresa Niccoli, Javier Gilbert‐Jaramillo, Samir Abdelkarim, Emma L Clayton, Mica Clarke, Marie‐Therese Konrad, Andrew J Nicoll, Jamie S Mitchell, Andrea Calvo, Adriano Chio, Henry Houlden, James M Polke, Mohamed A Ismail, Chad E Stephens, Tam Vo, Abdelbasset A Farahat, W D
Published in: EMBO Molecular Medicine, Issue 10/1, 2018, Page(s) 22-31, ISSN 1757-4676
Publisher: John Wiley & Sons Ltd.
DOI: 10.15252/emmm.201707850

A zebrafish model for C9orf72 ALS reveals RNA toxicity as a pathogenic mechanism

Author(s): Bart Swinnen, Andre Bento-Abreu, Tania F. Gendron, Steven Boeynaems, Elke Bogaert, Rik Nuyts, Mieke Timmers, Wendy Scheveneels, Nicole Hersmus, Jiou Wang, Sarah Mizielinska, Adrian M. Isaacs, Leonard Petrucelli, Robin Lemmens, Philip Van Damme, Ludo Van Den Bosch, Wim Robberecht
Published in: Acta Neuropathologica, Issue 135/3, 2018, Page(s) 427-443, ISSN 0001-6322
Publisher: Springer Verlag
DOI: 10.1007/s00401-017-1796-5

Specific biomarkers for C9orf72 FTD/ALS could expedite the journey towards effective therapies

Author(s): Rubika Balendra, Thomas G Moens, Adrian M Isaacs
Published in: EMBO Molecular Medicine, Issue 9/7, 2017, Page(s) 853-855, ISSN 1757-4676
Publisher: John Wiley & Sons Ltd.
DOI: 10.15252/emmm.201707848

Genetic models of C9orf72 : what is toxic?

Author(s): Thomas G Moens, Linda Partridge, Adrian M Isaacs
Published in: Current Opinion in Genetics & Development, Issue 44, 2017, Page(s) 92-101, ISSN 0959-437X
Publisher: Elsevier BV
DOI: 10.1016/j.gde.2017.01.006

SRSF1-dependent nuclear export inhibition of C9ORF72 repeat transcripts prevents neurodegeneration and associated motor deficits

Author(s): Guillaume M. Hautbergue, Lydia M. Castelli, Laura Ferraiuolo, Alvaro Sanchez-Martinez, Johnathan Cooper-Knock, Adrian Higginbottom, Ya-Hui Lin, Claudia S. Bauer, Jennifer E. Dodd, Monika A. Myszczynska, Sarah M. Alam, Pierre Garneret, Jayanth S. Chandran, Evangelia Karyka, Matthew J. Stopford, Emma F. Smith, Janine Kirby, Kathrin Meyer, Brian K. Kaspar, Adrian M. Isaacs, Sherif F. El-Khamisy, Kurt
Published in: Nature Communications, Issue 8, 2017, Page(s) 16063, ISSN 2041-1723
Publisher: Nature Publishing Group
DOI: 10.1038/ncomms16063

One target for amyotrophic lateral sclerosis therapy?

Author(s): S. Mizielinska, A. M. Isaacs
Published in: Science, Issue 353/6300, 2016, Page(s) 647-648, ISSN 0036-8075
Publisher: American Association for the Advancement of Science
DOI: 10.1126/science.aah5408

C9orf72 arginine-rich dipeptide proteins interact with ribosomal proteins in vivo to induce a toxic translational arrest that is rescued by eIF1A

Author(s): Thomas G. Moens, Teresa Niccoli, Katherine M. Wilson, Magda L. Atilano, Nicol Birsa, Lauren M. Gittings, Benedikt V. Holbling, Miranda C. Dyson, Annora Thoeng, Jacob Neeves, Idoia Glaria, Lu Yu, Julia Bussmann, Erik Storkebaum, Mercedes Pardo, Jyoti S. Choudhary, Pietro Fratta, Linda Partridge, Adrian M. Isaacs
Published in: Acta Neuropathologica, Issue 137/3, 2019, Page(s) 487-500, ISSN 0001-6322
Publisher: Springer Verlag
DOI: 10.1007/s00401-018-1946-4

Symmetric dimethylation of poly-GR correlates with disease duration in C9orf72 FTLD and ALS and reduces poly-GR phase separation and toxicity

Author(s): Lauren M. Gittings, Steven Boeynaems, Daniel Lightwood, Alison Clargo, Sarfaraj Topia, Lisa Nakayama, Claire Troakes, David M. A. Mann, Aaron D. Gitler, Tammaryn Lashley, Adrian M. Isaacs
Published in: Acta Neuropathologica, Issue 139/2, 2020, Page(s) 407-410, ISSN 0001-6322
Publisher: Springer Verlag
DOI: 10.1007/s00401-019-02104-x

Glycine-alanine dipeptide repeats spread rapidly in a repeat length- and age-dependent manner in the fly brain

Author(s): Javier Morón-Oset, Tessa Supèr, Jacqueline Esser, Adrian M. Isaacs, Sebastian Grönke, Linda Partridge
Published in: Acta Neuropathologica Communications, Issue 7/1, 2019, ISSN 2051-5960
Publisher: BioMed Central
DOI: 10.1186/s40478-019-0860-x

C9orf72-mediated ALS and FTD: multiple pathways to disease

Author(s): Rubika Balendra, Adrian M. Isaacs
Published in: Nature Reviews Neurology, Issue 14/9, 2018, Page(s) 544-558, ISSN 1759-4758
Publisher: Nature Publishing Group
DOI: 10.1038/s41582-018-0047-2

TDP-43 extracted from frontotemporal lobar degeneration subject brains displays distinct aggregate assemblies and neurotoxic effects reflecting disease progression rates

Author(s): Florent Laferrière, Zuzanna Maniecka, Manuela Pérez-Berlanga, Marian Hruska-Plochan, Larissa Gilhespy, Eva-Maria Hock, Ulrich Wagner, Tariq Afroz, Paul J. Boersema, Gery Barmettler, Sandrine C. Foti, Yasmine T. Asi, Adrian M. Isaacs, Ashraf Al-Amoudi, Amanda Lewis, Henning Stahlberg, John Ravits, Francesca De Giorgi, François Ichas, Erwan Bezard, Paola Picotti, Tammaryn Lashley, Magdalini Polym
Published in: Nature Neuroscience, Issue 22/1, 2019, Page(s) 65-77, ISSN 1097-6256
Publisher: Nature Publishing Group
DOI: 10.1038/s41593-018-0294-y

RPS25 is required for efficient RAN translation of C9orf72 and other neurodegenerative disease-associated nucleotide repeats

Author(s): Shizuka B. Yamada, Tania F. Gendron, Teresa Niccoli, Naomi R. Genuth, Rosslyn Grosely, Yingxiao Shi, Idoia Glaria, Nicholas J. Kramer, Lisa Nakayama, Shirleen Fang, Tai J. I. Dinger, Annora Thoeng, Gabriel Rocha, Maria Barna, Joseph D. Puglisi, Linda Partridge, Justin K. Ichida, Adrian M. Isaacs, Leonard Petrucelli, Aaron D. Gitler
Published in: Nature Neuroscience, Issue 22/9, 2019, Page(s) 1383-1388, ISSN 1097-6256
Publisher: Nature Publishing Group
DOI: 10.1038/s41593-019-0455-7

Quantitative analysis of cryptic splicing associated with TDP-43 depletion

Author(s): Jack Humphrey, Warren Emmett, Pietro Fratta, Adrian M. Isaacs, Vincent Plagnol
Published in: BMC Medical Genomics, Issue 10/1, 2017, ISSN 1755-8794
Publisher: BioMed Central
DOI: 10.1186/s12920-017-0274-1

Mice with endogenous TDP ‐43 mutations exhibit gain of splicing function and characteristics of amyotrophic lateral sclerosis

Author(s): Pietro Fratta, Prasanth Sivakumar, Jack Humphrey, Kitty Lo, Thomas Ricketts, Hugo Oliveira, Jose M Brito‐Armas, Bernadett Kalmar, Agnieszka Ule, Yichao Yu, Nicol Birsa, Cristian Bodo, Toby Collins, Alexander E Conicella, Alan Mejia Maza, Alessandro Marrero‐Gagliardi, Michelle Stewart, Joffrey Mianne, Silvia Corrochano, Warren Emmett, Gemma Codner, Michael Groves, Ryutaro Fukumura, Yoichi Gondo
Published in: The EMBO Journal, Issue 37/11, 2018, ISSN 0261-4189
Publisher: Nature Publishing Group
DOI: 10.15252/embj.201798684

Non-peer reviewed articles (2)

Relax, Don’t RAN Translate It

Author(s): Katherine M. Wilson, Bhavana Muralidharan, Adrian M. Isaacs
Published in: Neuron, Issue 104/5, 2019, Page(s) 827-829, ISSN 0896-6273
Publisher: Cell Press
DOI: 10.1016/j.neuron.2019.11.014

The snowball effect of RNA binding protein dysfunction in amyotrophic lateral sclerosis

Author(s): Pietro Fratta, Adrian M Isaacs
Published in: Brain, Issue 141/5, 2018, Page(s) 1236-1238, ISSN 0006-8950
Publisher: Oxford University Press
DOI: 10.1093/brain/awy091