000063153 001__ 63153
000063153 005__ 20190709135509.0
000063153 0247_ $$2doi$$a10.1038/s41467-017-00911-y
000063153 0248_ $$2sideral$$a101872
000063153 037__ $$aART-2017-101872
000063153 041__ $$aeng
000063153 100__ $$aGuo, Wenting
000063153 245__ $$aHDAC6 inhibition reverses axonal transport defects in motor neurons derived from FUS-ALS patients
000063153 260__ $$c2017
000063153 5060_ $$aAccess copy available to the general public$$fUnrestricted
000063153 5203_ $$aAmyotrophic 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.
000063153 540__ $$9info:eu-repo/semantics/openAccess$$aby$$uhttp://creativecommons.org/licenses/by/3.0/es/
000063153 590__ $$a12.353$$b2017
000063153 591__ $$aMULTIDISCIPLINARY SCIENCES$$b3 / 64 = 0.047$$c2017$$dQ1$$eT1
000063153 592__ $$a6.582$$b2017
000063153 593__ $$aBiochemistry, Genetics and Molecular Biology (miscellaneous)$$c2017$$dQ1
000063153 593__ $$aPhysics and Astronomy (miscellaneous)$$c2017$$dQ1
000063153 593__ $$aChemistry (miscellaneous)$$c2017$$dQ1
000063153 655_4 $$ainfo:eu-repo/semantics/article$$vinfo:eu-repo/semantics/publishedVersion
000063153 700__ $$aNaujock, Maximilian
000063153 700__ $$aFumagalli, Laura
000063153 700__ $$aVandoorne, Tijs
000063153 700__ $$aBaatsen, Pieter
000063153 700__ $$aBoon, Ruben
000063153 700__ $$0(orcid)0000-0003-3982-1263$$aOrdovás, Laura
000063153 700__ $$aPatel, Abdulsamie
000063153 700__ $$aWelters, Marc
000063153 700__ $$aVanwelden, Thomas
000063153 700__ $$aGeens, Natasja
000063153 700__ $$aTricot, Tine
000063153 700__ $$aBenoy, Veronick
000063153 700__ $$aSteyaert, Jolien
000063153 700__ $$aLefebvre-Omar, Cynthia
000063153 700__ $$aBoesmans, Werend
000063153 700__ $$aJarpe, Matthew
000063153 700__ $$aSterneckert, Jared
000063153 700__ $$aWegner, Florian
000063153 700__ $$aPetri, Susanne
000063153 700__ $$aBohl, Delphine
000063153 700__ $$aVanden Berghe, Pieter
000063153 700__ $$aRobberecht, Wim
000063153 700__ $$aVan Damme, Philip
000063153 700__ $$aVerfaillie, Catherine
000063153 700__ $$aVan Den Bosch, Ludo
000063153 773__ $$g8 (2017), 861 [15 pp]$$pNATURE COMMUNICATIONS$$tNature Communications$$x2041-1723
000063153 8564_ $$s5392760$$uhttps://zaguan.unizar.es/record/63153/files/texto_completo.pdf$$yVersión publicada
000063153 8564_ $$s87002$$uhttps://zaguan.unizar.es/record/63153/files/texto_completo.jpg?subformat=icon$$xicon$$yVersión publicada
000063153 909CO $$ooai:zaguan.unizar.es:63153$$particulos$$pdriver
000063153 951__ $$a2019-07-09-11:50:34
000063153 980__ $$aARTICLE