dc.contributor.author | Selvaraj, BT | en_US |
dc.contributor.author | Livesey, MR | en_US |
dc.contributor.author | Zhao, C | en_US |
dc.contributor.author | Gregory, JM | en_US |
dc.contributor.author | James, OT | en_US |
dc.contributor.author | Cleary, EM | en_US |
dc.contributor.author | Chouhan, AK | en_US |
dc.contributor.author | Gane, AB | en_US |
dc.contributor.author | Perkins, EM | en_US |
dc.contributor.author | Dando, O | en_US |
dc.contributor.author | Lillico, SG | en_US |
dc.contributor.author | Lee, Y-B | en_US |
dc.contributor.author | Nishimura, AL | en_US |
dc.contributor.author | Poreci, U | en_US |
dc.contributor.author | Thankamony, S | en_US |
dc.contributor.author | Pray, M | en_US |
dc.contributor.author | Vasistha, NA | en_US |
dc.contributor.author | Magnani, D | en_US |
dc.contributor.author | Borooah, S | en_US |
dc.contributor.author | Burr, K | en_US |
dc.contributor.author | Story, D | en_US |
dc.contributor.author | McCampbell, A | en_US |
dc.contributor.author | Shaw, CE | en_US |
dc.contributor.author | Kind, PC | en_US |
dc.contributor.author | Aitman, TJ | en_US |
dc.contributor.author | Whitelaw, CBA | en_US |
dc.contributor.author | Wilmut, I | en_US |
dc.contributor.author | Smith, C | en_US |
dc.contributor.author | Miles, GB | en_US |
dc.contributor.author | Hardingham, GE | en_US |
dc.contributor.author | Wyllie, DJA | en_US |
dc.contributor.author | Chandran, S | en_US |
dc.date.accessioned | 2024-01-02T15:40:52Z | |
dc.date.available | 2017-12-21 | en_US |
dc.date.issued | 2018-01-24 | en_US |
dc.identifier.uri | https://qmro.qmul.ac.uk/xmlui/handle/123456789/93262 | |
dc.description.abstract | Mutations in C9ORF72 are the most common cause of familial amyotrophic lateral sclerosis (ALS). Here, through a combination of RNA-Seq and electrophysiological studies on induced pluripotent stem cell (iPSC)-derived motor neurons (MNs), we show that increased expression of GluA1 AMPA receptor (AMPAR) subunit occurs in MNs with C9ORF72 mutations that leads to increased Ca2+-permeable AMPAR expression and results in enhanced selective MN vulnerability to excitotoxicity. These deficits are not found in iPSC-derived cortical neurons and are abolished by CRISPR/Cas9-mediated correction of the C9ORF72 repeat expansion in MNs. We also demonstrate that MN-specific dysregulation of AMPAR expression is also present in C9ORF72 patient post-mortem material. We therefore present multiple lines of evidence for the specific upregulation of GluA1 subunits in human mutant C9ORF72 MNs that could lead to a potential pathogenic excitotoxic mechanism in ALS. | en_US |
dc.format.extent | 347 - ? | en_US |
dc.language | eng | en_US |
dc.relation.ispartof | Nat Commun | en_US |
dc.rights | Attribution 3.0 United States | * |
dc.rights.uri | http://creativecommons.org/licenses/by/3.0/us/ | * |
dc.subject | Amyotrophic Lateral Sclerosis | en_US |
dc.subject | C9orf72 Protein | en_US |
dc.subject | CRISPR-Cas Systems | en_US |
dc.subject | Calcium | en_US |
dc.subject | DNA Repeat Expansion | en_US |
dc.subject | Gene Targeting | en_US |
dc.subject | Humans | en_US |
dc.subject | Motor Neurons | en_US |
dc.subject | Receptors, AMPA | en_US |
dc.subject | Spinal Cord | en_US |
dc.title | C9ORF72 repeat expansion causes vulnerability of motor neurons to Ca2+-permeable AMPA receptor-mediated excitotoxicity. | en_US |
dc.type | Article | |
dc.identifier.doi | 10.1038/s41467-017-02729-0 | en_US |
pubs.author-url | https://www.ncbi.nlm.nih.gov/pubmed/29367641 | en_US |
pubs.issue | 1 | en_US |
pubs.notes | Not known | en_US |
pubs.publication-status | Published online | en_US |
pubs.volume | 9 | en_US |
dcterms.dateAccepted | 2017-12-21 | en_US |
rioxxterms.funder | Default funder | en_US |
rioxxterms.identifier.project | Default project | en_US |