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Human iPSC-derived motoneurons harbouring TARDBP or C9ORF72 ALS mutations are dysfunctional despite maintaining viability
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dc.contributor.author | Devlin, Anna-Claire | |
dc.contributor.author | Burr, Karen | |
dc.contributor.author | Borooah, Shyamanga | |
dc.contributor.author | Foster, Joshua D | |
dc.contributor.author | Cleary, Elaine M | |
dc.contributor.author | Geti, Imbisaat | |
dc.contributor.author | Vallier, Ludovic | |
dc.contributor.author | Shaw, Christopher E | |
dc.contributor.author | Chandran, Siddharthan | |
dc.contributor.author | Miles, Gareth B | |
dc.date.accessioned | 2015-01-13T13:31:02Z | |
dc.date.available | 2015-01-13T13:31:02Z | |
dc.date.issued | 2015-01-12 | |
dc.identifier | 161787505 | |
dc.identifier | bb4d1a4d-0138-4465-aed9-5a80eade4dc0 | |
dc.identifier | 25580746 | |
dc.identifier | 84923091694 | |
dc.identifier | 000348829500006 | |
dc.identifier.citation | Devlin , A-C , Burr , K , Borooah , S , Foster , J D , Cleary , E M , Geti , I , Vallier , L , Shaw , C E , Chandran , S & Miles , G B 2015 , ' Human iPSC-derived motoneurons harbouring TARDBP or C9ORF72 ALS mutations are dysfunctional despite maintaining viability ' , Nature Communications , vol. 6 , 5999 . https://doi.org/10.1038/ncomms6999 | en |
dc.identifier.issn | 2041-1723 | |
dc.identifier.other | ORCID: /0000-0002-8624-4625/work/29135005 | |
dc.identifier.uri | https://hdl.handle.net/10023/5992 | |
dc.description | This work has been supported by: Motor Neurone Disease Association (G.B.M., S.C. and C.E.S.); Euan MacDonald Centre (G.B.M. and S.C.); European Research Council (L.V.); Cambridge Hospitals National Institute for Health Research Biomedical Research Center (L.V.). | en |
dc.description.abstract | Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease for which a greater understanding of early disease mechanisms is needed to reveal novel therapeutic targets. We report the use of human induced pluripotent stem cell (iPSC)-derived motoneurons (MNs) to study the pathophysiology of ALS. We demonstrate that MNs derived from iPSCs obtained from healthy individuals or patients harbouring TARDBP or C9ORF72 ALS-causing mutations are able to develop appropriate physiological properties. However, patient iPSC-derived MNs, independent of genotype, display an initial hyperexcitability followed by progressive loss of action potential output and synaptic activity. This loss of functional output reflects a progressive decrease in voltage-activated Na+ and K+ currents, which occurs in the absence of overt changes in cell viability. These data implicate early dysfunction or loss of ion channels as a convergent point that may contribute to the initiation of downstream degenerative pathways that ultimately lead to MN loss in ALS. | |
dc.format.extent | 12 | |
dc.format.extent | 1955525 | |
dc.language.iso | eng | |
dc.relation.ispartof | Nature Communications | en |
dc.subject | RC0321 Neuroscience. Biological psychiatry. Neuropsychiatry | en |
dc.subject | NDAS | en |
dc.subject | BDC | en |
dc.subject | R2C | en |
dc.subject | SDG 3 - Good Health and Well-being | en |
dc.subject.lcc | RC0321 | en |
dc.title | Human iPSC-derived motoneurons harbouring TARDBP or C9ORF72 ALS mutations are dysfunctional despite maintaining viability | en |
dc.type | Journal article | en |
dc.contributor.sponsor | Motor Neurone Disease Association | en |
dc.contributor.sponsor | Edinburgh University | en |
dc.contributor.institution | University of St Andrews. School of Psychology and Neuroscience | en |
dc.contributor.institution | University of St Andrews. Institute of Behavioural and Neural Sciences | en |
dc.identifier.doi | 10.1038/ncomms6999 | |
dc.description.status | Peer reviewed | en |
dc.identifier.url | https://www.nature.com/articles/ncomms6999#Sec18 | en |
dc.identifier.grantnumber | Miles/Oct12/6290 | en |
dc.identifier.grantnumber | N/A | en |
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