Correction: A rare missense variant impacting NEK1 kinase function is associated with ALS
Acta Neuropathologica Communications, vol. 14
Abstract
Correction: Acta Neuropathol Commun 14, 135 (2026)https://doi.org/10.1186/s40478-026-02351-6In this article [1], the figure citations for Figs. 4 and 5, and 6 in the paragraph “Notably, while NEK1 kinase activity has been proposed. translocation in control MNs” were incorrect.Notably, while NEK1 kinase activity has been proposed as the principal pathomechanism in NEK1-ALS [8], this hypothesis still required in vivo confirmation. NEK1 p.N598S MN cultures exhibited increased susceptibility to DNA damage and ciliary abnormalities (Fig. 4C-G), both processes known to depend on NEK1 kinase function [9, 15]. This led us to hypothesize that the p.N598S variant might directly impact NEK1 kinase activity. To test this, we quantified the phosphorylation of the established direct NEK1 target YAP1 at tyrosine 407 (pTyr407) [16]. Both p.N598S- and p.R812*-mutant MN cultures showed reduced YAP1 pTyr407 levels compared with their isogenic counterpart (Fig. 5A), supporting reduced kinase activity. This was further assessed in whole lysates from MN cultures, and in immunopurified NEK1-WT and p.N598S. Overall kinase activity was markedly reduced in both p.N598S- and p.R812*-mutant cultures compared to wild-type MNs (Fig. 5B). Direct measurement of purified NEK1 confirmed that the p.N598S variant displayed reduced kinase activity compared with wild-type NEK1 (Fig. 5C).To further establish causality, we treated MNs derived from three healthy donors with the NEK1-specific inhibitor BSc5367. Exposure to 11.5 nM BSc5367 for 48 h significantly reduced kinase activity (Fig. 6A), decreased YAP1 phosphorylation at Tyr407 (Fig. 6B), and increased γH2A.X levels (Fig. 6C). Most notably, pharmacological inhibition of NEK1 was also sufficient to induce TDP- 43 nucleocytoplasmic translocation in control MNs (Fig. 6D).These citations have now been corrected in the original publication.The original article has been corrected.
Authors 31
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Dávid Brenner corresponding
Universität Ulm · German Center for Neurodegenerative Diseases · University Hospital Ulm
Affiliation as printed
Center for Rare Diseases (ZSE) Ulm, Ulm University Hospital Center for Rare Diseases, Ulm, 89081, Germany. david.brenner@uni-ulm.de
Department of Neurology, University Hospital Ulm, 89081, Ulm, Germany. david.brenner@uni-ulm.de
German Center for Neurodegenerative Diseases (DZNE), Ulm site, Ulm, 89081, Germany. david.brenner@uni-ulm.de
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Affiliation as printed
Institute of Anatomy and Cell Biology, Ulm University School of Medicine, Ulm, 89081, Germany
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Affiliation as printed
Institute of Anatomy and Cell Biology, Ulm University School of Medicine, Ulm, 89081, Germany
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Affiliation as printed
Institute of Anatomy and Cell Biology, Ulm University School of Medicine, Ulm, 89081, Germany
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VIB-KU Leuven Center for Brain & Disease Research · KU Leuven
Affiliation as printed
Department of Neurosciences, Laboratory of Neurobiology and Leuven Brain Institute (LBI), KU Leuven-University of Leuven, Leuven, 3000, Belgium
VIB, Center for Brain & Disease Research, Leuven, 3001, Belgium
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Affiliation as printed
Department of Neurology, University Hospital Ulm, 89081, Ulm, Germany
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Universitätsklinikum Aachen · RWTH Aachen University
Affiliation as printed
Institute of Neuropathology, RWTH Aachen University Hospital, Pauwelsstrasse 30, Aachen, 52074, Germany
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Affiliation as printed
Biomedical Informatics, Data Mining and Data Analytics, University of Augsburg, Augsburg, 86159, Germany
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Universität Ulm · University Hospital Ulm
Affiliation as printed
Institute of Molecular Oncology and Stem Cell Biology (IMOS), Ulm University Hospital, Ulm, 89081, Germany
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Affiliation as printed
Biomedical Informatics, Data Mining and Data Analytics, University of Augsburg, Augsburg, 86159, Germany
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Universitätsklinikum Aachen · RWTH Aachen University
Affiliation as printed
Institute of Neuropathology, RWTH Aachen University Hospital, Pauwelsstrasse 30, Aachen, 52074, Germany
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VIB-KU Leuven Center for Brain & Disease Research · KU Leuven
Affiliation as printed
Department of Neurosciences, Laboratory of Neurobiology and Leuven Brain Institute (LBI), KU Leuven-University of Leuven, Leuven, 3000, Belgium
VIB, Center for Brain & Disease Research, Leuven, 3001, Belgium
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Johns Hopkins University · Universität Ulm · Johns Hopkins Medicine
Affiliation as printed
Brain Science Institute, Johns Hopkins University School of Medicine, Baltimore, MD, USA
Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, USA
Institute of Anatomy and Cell Biology, Ulm University School of Medicine, Ulm, 89081, Germany
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Affiliation as printed
Department of Neurology, Centre for ALS and Other Motor Neuron Disorders, Alfried Krupp Krankenhaus Rüttenscheid, Essen, 45131, Germany
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Affiliation as printed
Department of Neurology, University Hospital Ulm, 89081, Ulm, Germany
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German Center for Neurodegenerative Diseases · University Hospital Ulm
Affiliation as printed
Department of Neurology, University Hospital Ulm, 89081, Ulm, Germany
German Center for Neurodegenerative Diseases (DZNE), Ulm site, Ulm, 89081, Germany
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Affiliation as printed
Institute of Human Genetics, Ulm University and Ulm University Medical Center, Ulm, Germany
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Universität Ulm · University Hospital Ulm
Affiliation as printed
Center for Rare Diseases (ZSE) Ulm, Ulm University Hospital Center for Rare Diseases, Ulm, 89081, Germany
Core Facility Organoids, Ulm University, Ulm, 89081, Germany
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Universität Ulm · German Center for Neurodegenerative Diseases
Affiliation as printed
German Center for Neurodegenerative Diseases (DZNE), Ulm site, Ulm, 89081, Germany
Institute of Anatomy and Cell Biology, Ulm University School of Medicine, Ulm, 89081, Germany
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Utrecht University · University Medical Center Utrecht
Affiliation as printed
Department of Neurology, Brain Centre Rudolf Magnus, University Medical Centre Utrecht, Utrecht University, Utrecht, 3584 CG, The Netherlands
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Utrecht University · University Medical Center Utrecht
Affiliation as printed
Department of Neurology, Brain Centre Rudolf Magnus, University Medical Centre Utrecht, Utrecht University, Utrecht, 3584 CG, The Netherlands
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Universität Ulm · University Hospital Ulm
Affiliation as printed
Center for Rare Diseases (ZSE) Ulm, Ulm University Hospital Center for Rare Diseases, Ulm, 89081, Germany
Core Facility Organoids, Ulm University, Ulm, 89081, Germany
Department of Internal Medicine I, Division of Interdisciplinary Pancreatology, Ulm University Hospital, Ulm, 89081, Germany
Institute of Molecular Oncology and Stem Cell Biology (IMOS), Ulm University Hospital, Ulm, 89081, Germany
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Affiliation as printed
Medical Faculty, Unit for Single-Cell Genomics, Ulm University, Ulm, 89081, Germany
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Affiliation as printed
Department of Clinical Sciences, Neurosciences, Umeå University , Umeå, Sweden
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Affiliation as printed
Department of Clinical Sciences, Neurosciences, Umeå University , Umeå, Sweden
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Universität Ulm · German Center for Neurodegenerative Diseases · University Hospital Ulm
Affiliation as printed
Center for Rare Diseases (ZSE) Ulm, Ulm University Hospital Center for Rare Diseases, Ulm, 89081, Germany
Department of Neurology, University Hospital Ulm, 89081, Ulm, Germany
German Center for Neurodegenerative Diseases (DZNE), Ulm site, Ulm, 89081, Germany
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Affiliation as printed
Department of Neurology, University Hospital Ulm, 89081, Ulm, Germany
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Affiliation as printed
Department of Neurology, Centre for ALS and Other Motor Neuron Disorders, Alfried Krupp Krankenhaus Rüttenscheid, Essen, 45131, Germany
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Universitair Ziekenhuis Leuven · KU Leuven
Affiliation as printed
Department of Neurology, University Hospitals Leuven, Leuven, 3000, Belgium
Department of Neurosciences, Laboratory of Neurobiology and Leuven Brain Institute (LBI), KU Leuven-University of Leuven, Leuven, 3000, Belgium
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Universitätsklinikum Aachen · RWTH Aachen University
Affiliation as printed
Institute of Neuropathology, RWTH Aachen University Hospital, Pauwelsstrasse 30, Aachen, 52074, Germany
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Universität Ulm · German Center for Neurodegenerative Diseases · Universitätsklinikum Aachen · RWTH Aachen University
Affiliation as printed
German Center for Neurodegenerative Diseases (DZNE), Ulm site, Ulm, 89081, Germany. acatanese@ukaachen.de
Institute of Anatomy and Cell Biology, Ulm University School of Medicine, Ulm, 89081, Germany. acatanese@ukaachen.de
Institute of Neuroanatomy, University Clinic RWTH Aachen, Wendlingweg 2, Aachen, 52074, Germany. acatanese@ukaachen.de
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