Dose imbalance of DYRK1A kinase causes systemic progeroid status in Down syndrome by increasing the un-repaired DNA damage and reducing LaminB1 levels

People with Down syndrome (DS) show clinical signs of accelerated ageing. Causative mechanisms remain unknown and hypotheses range from the (essentially untreatable) amplified-chromosomal-instability explanation, to potential actions of individual supernumerary chromosome-21 genes. The latter explan...

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Main Authors: Murray, Aoife, Gough, Gillian, Cindrić, Ana, Vučković, Frano, Koschut, David, Borelli, Vincenzo, Petrović, Dražen J., Bekavac, Ana, Plećaš, Ante, Hribljan, Valentina, Brunmeir, Reinhard, Jurić, Julija, Pučić-Baković, Maja, Slana, Anita, Deriš, Helena, Frkatović, Azra, Groet, Jűrgen, O'Brien, Niamh L., Chen, Hong Yu, Yeap, Yee Jie, Delom, Frederic, Havlicek, Steven, Gammon, Luke, Hamburg, Sarah, Startin, Carla, D'Souza, Hana, Mitrečić, Dinko, Kero, Mijana, Odak, Ljubica, Krušlin, Božo, Krsnik, Željka, Kostović, Ivica, Foo, Jia Nee, Loh, Yuin-Han, Dunn, Norris Ray, de la Luna, Susana, Spector, Tim, Barišić, Ingeborg, Thomas, Michael S. C., Strydom, Andre, Franceschi, Claudio, Lauc, Gordan, Krištić, Jasminka, Alić, Ivan, Nizetic, Dean
Other Authors: Lee Kong Chian School of Medicine (LKCMedicine)
Format: Article
Language:English
Published: 2023
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Online Access:https://hdl.handle.net/10356/171675
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Institution: Nanyang Technological University
Language: English
Description
Summary:People with Down syndrome (DS) show clinical signs of accelerated ageing. Causative mechanisms remain unknown and hypotheses range from the (essentially untreatable) amplified-chromosomal-instability explanation, to potential actions of individual supernumerary chromosome-21 genes. The latter explanation could open a route to therapeutic amelioration if the specific over-acting genes could be identified and their action toned-down.