Nature Communications (Jan 2018)
Impaired DNA damage response signaling by FUS-NLS mutations leads to neurodegeneration and FUS aggregate formation
- Marcel Naumann,
- Arun Pal,
- Anand Goswami,
- Xenia Lojewski,
- Julia Japtok,
- Anne Vehlow,
- Maximilian Naujock,
- René Günther,
- Mengmeng Jin,
- Nancy Stanslowsky,
- Peter Reinhardt,
- Jared Sterneckert,
- Marie Frickenhaus,
- Francisco Pan-Montojo,
- Erik Storkebaum,
- Ina Poser,
- Axel Freischmidt,
- Jochen H. Weishaupt,
- Karlheinz Holzmann,
- Dirk Troost,
- Albert C. Ludolph,
- Tobias M. Boeckers,
- Stefan Liebau,
- Susanne Petri,
- Nils Cordes,
- Anthony A. Hyman,
- Florian Wegner,
- Stephan W. Grill,
- Joachim Weis,
- Alexander Storch,
- Andreas Hermann
Affiliations
- Marcel Naumann
- Department of Neurology, Technische Universität Dresden
- Arun Pal
- Department of Neurology, Technische Universität Dresden
- Anand Goswami
- Institute of Neuropathology, RWTH Aachen University Hospital
- Xenia Lojewski
- Department of Neurology, Technische Universität Dresden
- Julia Japtok
- Department of Neurology, Technische Universität Dresden
- Anne Vehlow
- OncoRay—National Center for Radiation Research in Oncology, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Helmholtz-Zentrum Dresden-Rossendorf
- Maximilian Naujock
- Department of Neurology, Hannover Medical School
- René Günther
- Department of Neurology, Technische Universität Dresden
- Mengmeng Jin
- Department of Neurology, Technische Universität Dresden
- Nancy Stanslowsky
- Department of Neurology, Hannover Medical School
- Peter Reinhardt
- Center for Regenerative Therapies Dresden (CRTD), Technische Universität Dresden
- Jared Sterneckert
- Center for Regenerative Therapies Dresden (CRTD), Technische Universität Dresden
- Marie Frickenhaus
- Molecular Neurogenetics Laboratory, Max Planck Institute for Molecular Biomedicine
- Francisco Pan-Montojo
- Department of Neurology, Klinikum der Universität München, and Munich Cluster for Systems Neurology
- Erik Storkebaum
- Molecular Neurogenetics Laboratory, Max Planck Institute for Molecular Biomedicine
- Ina Poser
- Max Planck Institute of Molecular Cell Biology and Genetics
- Axel Freischmidt
- Department of Neurology, University Ulm
- Jochen H. Weishaupt
- Department of Neurology, University Ulm
- Karlheinz Holzmann
- Genomics-Core Facility, University Hospital Ulm, Centre for Biomedical Research
- Dirk Troost
- Division of Neuropathology, Department of Pathology, Academic Medical Centre
- Albert C. Ludolph
- Department of Neurology, University Ulm
- Tobias M. Boeckers
- Institute of Anatomy and Cell Biology, University of Ulm
- Stefan Liebau
- Institute of Neuroanatomy & Developmental Biology, Eberhard Karls University of Tübingen
- Susanne Petri
- Department of Neurology, Hannover Medical School
- Nils Cordes
- OncoRay—National Center for Radiation Research in Oncology, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Helmholtz-Zentrum Dresden-Rossendorf
- Anthony A. Hyman
- Max Planck Institute of Molecular Cell Biology and Genetics
- Florian Wegner
- Department of Neurology, Hannover Medical School
- Stephan W. Grill
- Max Planck Institute of Molecular Cell Biology and Genetics
- Joachim Weis
- Institute of Neuropathology, RWTH Aachen University Hospital
- Alexander Storch
- Department of Neurology, Technische Universität Dresden
- Andreas Hermann
- Department of Neurology, Technische Universität Dresden
- DOI
- https://doi.org/10.1038/s41467-017-02299-1
- Journal volume & issue
-
Vol. 9,
no. 1
pp. 1 – 17
Abstract
Abnormal cytoplasmic aggregates of FUS are a hallmark of some forms of amyotrophic lateral sclerosis (ALS). Here, using neurons derived from patients with FUS-ALS, the authors demonstrate that impairment of PARP-dependent DNA damage signaling is an event that occurs upstream of neurodegeneration and cytoplasmic aggregate formation in FUS-ALS.
