Year: 2026
Type: erratum
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: David Brenner, Anna Ponomarenko, Iris Petrut, Sofia Beyrle, Matilde Contardo, Isabel Loss, Constantin Radke, Jonas Frank, Eleni Zimmer, Matthias Schlesner, Pascal Achenbach, Wendy Scheveneels, Amr Aly, Hülya Nazlican, Jasper Hesebeck-Brinkmann, Patrick Oeckl, Kathrin Müller, Reiner Siebert, Tobias Böckers, Kristel van Eijk, Jan Veldink, Alexander Kleger, Medhanie Mulaw, Peter M. Andersen, Karin Forsberg, Jochen H. Weishaupt, Seyed Babak Loghmani, Thorsten Grehl, Philip van Damme, Joachim Weis, Alberto Catanese
Institutions: Universität Ulm, German Center for Neurodegenerative Diseases, University Hospital Ulm, VIB-KU Leuven Center for Brain & Disease Research, KU Leuven, Universitätsklinikum Aachen, RWTH Aachen University, University of Augsburg, Johns Hopkins University, Johns Hopkins Medicine, Alfried Krupp Hospital, Utrecht University, University Medical Center Utrecht, Umeå University, Universitair Ziekenhuis Leuven
Language: English
Subfield: Neurology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $3,790
Award: G885172923
OpenAlex ID: W7169805384