dc.contributor.author | Bilican, B | |
dc.contributor.author | Serio, A | |
dc.contributor.author | Barmada, SJ | |
dc.contributor.author | Nishimura, AL | |
dc.contributor.author | Sullivan, GJ | |
dc.contributor.author | Carrasco, M | |
dc.contributor.author | Phatnani, HP | |
dc.contributor.author | Puddifoot, CA | |
dc.contributor.author | Story, D | |
dc.contributor.author | Fletcher, J | |
dc.contributor.author | Park, I-H | |
dc.contributor.author | Friedman, BA | |
dc.contributor.author | Daley, GQ | |
dc.contributor.author | Wyllie, DJA | |
dc.contributor.author | Hardingham, GE | |
dc.contributor.author | Wilmut, I | |
dc.contributor.author | Finkbeiner, S | |
dc.contributor.author | Maniatis, T | |
dc.contributor.author | Shaw, CE | |
dc.contributor.author | Chandran, S | |
dc.date.accessioned | 2024-01-04T15:07:30Z | |
dc.date.available | 2024-01-04T15:07:30Z | |
dc.date.issued | 2012-03-26 | |
dc.identifier.uri | https://qmro.qmul.ac.uk/xmlui/handle/123456789/93392 | |
dc.description.abstract | Transactive response DNA-binding (TDP-43) protein is the dominant disease protein in amyotrophic lateral sclerosis (ALS) and a subgroup of frontotemporal lobar degeneration (FTLD-TDP). Identification of mutations in the gene encoding TDP-43 (TARDBP) in familial ALS confirms a mechanistic link between misaccumulation of TDP-43 and neurodegeneration and provides an opportunity to study TDP-43 proteinopathies in human neurons generated from patient fibroblasts by using induced pluripotent stem cells (iPSCs). Here, we report the generation of iPSCs that carry the TDP-43 M337V mutation and their differentiation into neurons and functional motor neurons. Mutant neurons had elevated levels of soluble and detergent-resistant TDP-43 protein, decreased survival in longitudinal studies, and increased vulnerability to antagonism of the PI3K pathway. We conclude that expression of physiological levels of TDP-43 in human neurons is sufficient to reveal a mutation-specific cell-autonomous phenotype and strongly supports this approach for the study of disease mechanisms and for drug screening. | en_US |
dc.format.extent | 5803 - 5808 | |
dc.language | eng | |
dc.publisher | National Academy of Sciences | en_US |
dc.relation.ispartof | Proc Natl Acad Sci U S A | |
dc.subject | Adult | en_US |
dc.subject | Cell Differentiation | en_US |
dc.subject | DNA-Binding Proteins | en_US |
dc.subject | Detergents | en_US |
dc.subject | Female | en_US |
dc.subject | Fibroblasts | en_US |
dc.subject | Humans | en_US |
dc.subject | Induced Pluripotent Stem Cells | en_US |
dc.subject | Male | en_US |
dc.subject | Middle Aged | en_US |
dc.subject | Motor Neurons | en_US |
dc.subject | Mutation | en_US |
dc.subject | Organ Specificity | en_US |
dc.subject | Solubility | en_US |
dc.subject | TDP-43 Proteinopathies | en_US |
dc.title | Mutant induced pluripotent stem cell lines recapitulate aspects of TDP-43 proteinopathies and reveal cell-specific vulnerability | en_US |
dc.type | Article | en_US |
dc.identifier.doi | 10.1073/pnas.1202922109 | |
pubs.author-url | https://www.ncbi.nlm.nih.gov/pubmed/22451909 | en_US |
pubs.issue | 15 | en_US |
pubs.notes | Not known | en_US |
pubs.publication-status | Published | en_US |
pubs.volume | 109 | en_US |
rioxxterms.funder | Default funder | en_US |
rioxxterms.identifier.project | Default project | en_US |