C9orf72 -derived arginine-containing dipeptide repeats associate with axonal transport machinery and impede microtubule-based motility

Author:

Fumagalli Laura12ORCID,Young Florence L.3ORCID,Boeynaems Steven4ORCID,De Decker Mathias12,Mehta Arpan R.5678ORCID,Swijsen Ann12,Fazal Raheem12ORCID,Guo Wenting129ORCID,Moisse Matthieu12ORCID,Beckers Jimmy12,Dedeene Lieselot12101112ORCID,Selvaraj Bhuvaneish T.568ORCID,Vandoorne Tijs12,Madan Vanesa3,van Blitterswijk Marka13ORCID,Raitcheva Denitza14ORCID,McCampbell Alexander14ORCID,Poesen Koen1012,Gitler Aaron D.4ORCID,Koch Philipp1516ORCID,Berghe Pieter Vanden17ORCID,Thal Dietmar Rudolf1118ORCID,Verfaillie Catherine9ORCID,Chandran Siddharthan567819,Van Den Bosch Ludo12ORCID,Bullock Simon L.3ORCID,Van Damme Philip1220ORCID

Affiliation:

1. KU Leuven—University of Leuven, Department of Neurosciences, Experimental Neurology and Leuven Brain Institute (LBI), Leuven, Belgium.

2. VIB, Center for Brain & Disease Research, Laboratory of Neurobiology, Leuven, Belgium.

3. Division of Cell Biology, MRC Laboratory of Molecular Biology, Cambridge, UK.

4. Department of Genetics, Stanford University School of Medicine, Stanford, CA, USA.

5. UK Dementia Research Institute, University of Edinburgh, Edinburgh, UK.

6. Centre for Clinical Brain Sciences, University of Edinburgh, Edinburgh, UK.

7. The Anne Rowling Regenerative Neurology Clinic, University of Edinburgh, Edinburgh, UK.

8. The Euan MacDonald Centre, University of Edinburgh, Edinburgh, UK.

9. KU Leuven—University of Leuven, Department of Development and Regeneration, Stem Cell Institute, Leuven, Belgium.

10. KU Leuven—University of Leuven, Department of Neurosciences, Laboratory for Molecular Neurobiomarker Research and Leuven Brain Institute (LBI), Leuven, Belgium.

11. KU Leuven—University of Leuven, Department of Imaging and Pathology, Laboratory for Neuropathology and Leuven Brain Institute (LBI), Leuven, Belgium.

12. Laboratory Medicine, University Hospitals Leuven, Leuven, Belgium.

13. Department of Neuroscience, Mayo Clinic, Jacksonville, FL, USA.

14. Biogen Idec, Boston, MA, USA.

15. Hector Institute for Translational Brain Research, Central Institute of Mental Health, University of Heidelberg, Heidelberg, Germany.

16. Institute of Reconstructive Neurobiology, Life & Brain Center, University of Bonn, Bonn, Germany.

17. KU Leuven—University of Leuven, Translational Research Centre for Gastrointestinal Disorders, Leuven, Belgium.

18. Department of Pathology, University Hospitals Leuven, Leuven, Belgium.

19. Centre for Brain Development and Repair, inStem, Bangalore, India.

20. Department of Neurology, University Hospitals Leuven, Leuven, Belgium.

Abstract

Arginine-rich dipeptide repeats associated with ALS and FTD inhibit machinery for microtubule-based axonal cargo transport.

Funder

Medical Research Council

Motor Neurone Disease Association

Fonds Wetenschappelijk Onderzoek

Japan Fisheries Research and Education Agency

Vlaamse regering

Agentschap voor Innovatie door Wetenschap en Technologie

Medical Research Council Canada

Vlaams Instituut voor Biotechnologie

Center for Life Sciences

Onderzoeksraad, KU Leuven

Koç Üniversitesi

Hellenic Society of Cardiology

Publisher

American Association for the Advancement of Science (AAAS)

Subject

Multidisciplinary

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