63153 20190709135509.0 doi 10.1038/s41467-017-00911-y sideral 101872 ART-2017-101872 eng Guo, Wenting HDAC6 inhibition reverses axonal transport defects in motor neurons derived from FUS-ALS patients 2017 Access copy available to the general public Unrestricted Amyotrophic lateral sclerosis (ALS) is a rapidly progressive neurodegenerative disorder due to selective loss of motor neurons (MNs). Mutations in the fused in sarcoma (FUS) gene can cause both juvenile and late onset ALS. We generated and characterized induced pluripotent stem cells (iPSCs) from ALS patients with different FUS mutations, as well as from healthy controls. Patient-derived MNs show typical cytoplasmic FUS pathology, hypoexcitability, as well as progressive axonal transport defects. Axonal transport defects are rescued by CRISPR/Cas9-mediated genetic correction of the FUS mutation in patient-derived iPSCs. Moreover, these defects are reproduced by expressing mutant FUS in human embryonic stem cells (hESCs), whereas knockdown of endogenous FUS has no effect, confirming that these pathological changes are mutant FUS dependent. Pharmacological inhibition as well as genetic silencing of histone deacetylase 6 (HDAC6) increase a-tubulin acetylation, endoplasmic reticulum (ER)-mitochondrial overlay, and restore the axonal transport defects in patient-derived MNs. info:eu-repo/semantics/openAccess by http://creativecommons.org/licenses/by/3.0/es/ 12.353 2017 MULTIDISCIPLINARY SCIENCES 3 / 64 = 0.047 2017 Q1 T1 6.582 2017 Biochemistry, Genetics and Molecular Biology (miscellaneous) 2017 Q1 Physics and Astronomy (miscellaneous) 2017 Q1 Chemistry (miscellaneous) 2017 Q1 info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion Naujock, Maximilian Fumagalli, Laura Vandoorne, Tijs Baatsen, Pieter Boon, Ruben (orcid)0000-0003-3982-1263 Ordovás, Laura Patel, Abdulsamie Welters, Marc Vanwelden, Thomas Geens, Natasja Tricot, Tine Benoy, Veronick Steyaert, Jolien Lefebvre-Omar, Cynthia Boesmans, Werend Jarpe, Matthew Sterneckert, Jared Wegner, Florian Petri, Susanne Bohl, Delphine Vanden Berghe, Pieter Robberecht, Wim Van Damme, Philip Verfaillie, Catherine Van Den Bosch, Ludo 8 (2017), 861 [15 pp] NATURE COMMUNICATIONS Nature Communications 2041-1723 5392760 http://zaguan.unizar.es/record/63153/files/texto_completo.pdf Versión publicada 87002 http://zaguan.unizar.es/record/63153/files/texto_completo.jpg?subformat=icon icon Versión publicada oai:zaguan.unizar.es:63153 articulos driver 2019-07-09-11:50:34 ARTICLE