CRISPR/Cas9 screen in human iPSC‐derived cortical neurons identifies NEK6 as a novel disease modifier of C9orf72 poly(PR) toxicity

Introduction The most common genetic cause of frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS) are hexanucleotide repeats in chromosome 9 open reading frame 72 (C9orf72). These repeats produce dipeptide repeat proteins with poly(PR) being the most toxic one. Methods We performed...

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Veröffentlicht in:	Alzheimer's & dementia 2023-04, Vol.19 (4), p.1245-1259
Hauptverfasser:	Guo, Wenting, Wang, Haibo, Kumar Tharkeshwar, Arun, Couthouis, Julien, Braems, Elke, Masrori, Pegah, Van Schoor, Evelien, Fan, Yannan, Ahuja, Karan, Moisse, Matthieu, Jacquemyn, Maarten, Furtado Madeiro da Costa, Rodrigo, Gajjar, Madhavsai, Balusu, Sriram, Tricot, Tine, Fumagalli, Laura, Hersmus, Nicole, Janky, Rekin's, Impens, Francis, Vanden Berghe, Pieter, Ho, Ritchie, Thal, Dietmar Rudolf, Vandenberghe, Rik, Hegde, Muralidhar L., Chandran, Siddharthan, De Strooper, Bart, Daelemans, Dirk, Van Damme, Philip, Van Den Bosch, Ludo, Verfaillie, Catherine
Format:	Artikel
Sprache:	eng
Schlagworte:	amyotrophic lateral sclerosis Amyotrophic Lateral Sclerosis - genetics Animals C9orf72 C9orf72 Protein - genetics CRISPR-Cas Systems CRISPR/Cas9 screen DNA damage DNA Repeat Expansion - genetics frontotemporal dementia Frontotemporal Dementia - genetics human pluripotent stem cells Humans Induced Pluripotent Stem Cells - metabolism NEK6 neurodegeneration Neurons - metabolism NIMA-Related Kinases - genetics NIMA-Related Kinases - metabolism p53 PR toxicity Tumor Suppressor Protein p53 - genetics Tumor Suppressor Protein p53 - metabolism Zebrafish - genetics Zebrafish - metabolism
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