prikaz prve stranice dokumenta Dose imbalance of DYRK1A kinase causes systemic progeroid status in Down syndrome by increasing the un-repaired DNA damage and reducing LaminB1 levels
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Dose imbalance of DYRK1A kinase causes systemic progeroid status in Down syndrome by increasing the un-repaired DNA damage and reducing LaminB1 levels
eBioMedicine, 94 (2023); 104692. https://doi.org/10.1016/j.ebiom.2023.104692
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; Nižetić, Dean Više autora...

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Murray, A., Gough, G., Cindrić, A., Vučković, F., Koschut, D., Borelli, V. ... Nižetić, D. (2023). Dose imbalance of DYRK1A kinase causes systemic progeroid status in Down syndrome by increasing the un-repaired DNA damage and reducing LaminB1 levels. eBioMedicine, 94.. doi: 10.1016/j.ebiom.2023.104692

Murray, Aoife, et al. "Dose imbalance of DYRK1A kinase causes systemic progeroid status in Down syndrome by increasing the un-repaired DNA damage and reducing LaminB1 levels." eBioMedicine, vol. 94, 2023. https://doi.org/10.1016/j.ebiom.2023.104692

Murray, Aoife, Gillian Gough, Ana Cindrić, Frano Vučković, David Koschut, Vincenzo Borelli, Dražen J. Petrović, et al. "Dose imbalance of DYRK1A kinase causes systemic progeroid status in Down syndrome by increasing the un-repaired DNA damage and reducing LaminB1 levels." eBioMedicine 94 (2023). https://doi.org/10.1016/j.ebiom.2023.104692

Murray, A., et al. (2023) 'Dose imbalance of DYRK1A kinase causes systemic progeroid status in Down syndrome by increasing the un-repaired DNA damage and reducing LaminB1 levels', eBioMedicine, 94. doi: 10.1016/j.ebiom.2023.104692

Murray A, Gough G, Cindrić A, Vučković F, Koschut D, Borelli V, i sur.. Dose imbalance of DYRK1A kinase causes systemic progeroid status in Down syndrome by increasing the un-repaired DNA damage and reducing LaminB1 levels. eBioMedicine [Internet]. 08.2023. [pristupljeno 26.09.2024.];94. doi: 10.1016/j.ebiom.2023.104692

A. Murray, et al., "Dose imbalance of DYRK1A kinase causes systemic progeroid status in Down syndrome by increasing the un-repaired DNA damage and reducing LaminB1 levels", eBioMedicine, vol. 94, Kolovoz 2023. [Online]. Dostupno na: https://urn.nsk.hr/urn:nbn:hr:105:015489. [Citirano: 26.09.2024.]

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Naslov (engleski)Dose imbalance of DYRK1A kinase causes systemic progeroid status in Down syndrome by increasing the un-repaired DNA damage and reducing LaminB1 levels
AutorAoife Murray
AutorGillian Gough
AutorAna Cindrić
AutorFrano Vučković
AutorDavid Koschut
AutorVincenzo Borelli
AutorDražen J. Petrović
AutorAna Bekavac
AutorAnte Plećaš
AutorValentina Hribljan
AutorReinhard Brunmeir
AutorJulija Jurić
AutorMaja Pučić-Baković
AutorAnita Slana
AutorHelena Deriš
AutorAzra Frkatović
AutorJűrgen Groet
AutorNiamh L. O’Brien
AutorHong Yu Chen
AutorYee Jie Yeap
AutorFrederic Delom
AutorSteven Havlicek
AutorLuke Gammon
AutorSarah Hamburg
AutorCarla Startin
AutorHana D’Souza
AutorDinko Mitrečić
AutorMijana Kero
AutorLjubica Odak
AutorBožo Krušlin
AutorŽeljka Krsnik
AutorIvica Kostović
AutorJia Nee Foo
AutorYuin-Han Loh
AutorNorris Ray Dunn
AutorSusana de la Luna
AutorTim Spector
AutorIngeborg Barišić
AutorMichael S.C. Thomas
AutorAndre Strydom
AutorClaudio Franceschi
AutorGordan Lauc
AutorJasminka Krištić
AutorIvan Alić
AutorDean Nižetić
Autorova ustanovaSveučilište u Zagrebu
Medicinski fakultet
(HRVATSKI INSTITUT ZA ISTRAŽIVANJE MOZGA)
Autorova ustanovaSveučilište u Zagrebu
Medicinski fakultet
(KATEDRA ZA HISTOLOGIJU I EMBRIOLOGIJU)
Autorova ustanovaSveučilište u Zagrebu
Medicinski fakultet
(KATEDRA ZA PATOLOGIJU)
Znanstveno / umjetničko
područje, polje i grana		BIOMEDICINA I ZDRAVSTVO
Temeljne medicinske znanosti
Citologija, histologija i embriologija
Znanstveno / umjetničko
područje, polje i grana		BIOMEDICINA I ZDRAVSTVO
Kliničke medicinske znanosti
Patologija
Sažetak (engleski)
Background: 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. Methods: Biological age was estimated through patterns of sugar molecules attached to plasma immunoglobulin-G (IgG-glycans, an established "biological-ageing-clock") in n = 246 individuals with DS from three European populations, clinically characterised for the presence of co-morbidities, and compared to n = 256 age-, sex- and demography-matched healthy controls. Isogenic human induced pluripotent stem cell (hiPSCs) models of full and partial trisomy-21 with CRISPR-Cas9 gene editing and two kinase inhibitors were studied prior and after differentiation to cerebral organoids. Findings: Biological age in adults with DS is (on average) 18.4-19.1 years older than in chronological-age-matched controls independent of co-morbidities, and this shift remains constant throughout lifespan. Changes are detectable from early childhood, and do not require a supernumerary chromosome, but are seen in segmental duplication of only 31 genes, along with increased DNA damage and decreased levels of LaminB1 in nucleated blood cells. We demonstrate that these cell-autonomous phenotypes can be gene-dose-modelled and pharmacologically corrected in hiPSCs and derived cerebral organoids. Using isogenic hiPSC models we show that chromosome-21 gene DYRK1A overdose is sufficient and necessary to cause excess unrepaired DNA damage. Interpretation: Explanation of hitherto observed accelerated ageing in DS as a developmental progeroid syndrome driven by DYRK1A overdose provides a target for early pharmacological preventative intervention strategies.
Ključne riječi (engleski)
Jezikengleski
Vrsta publikacijeZnanstveni rad - Izvorni znanstveni rad
Status objaveObjavljen
Vrsta recenzijeRecenziran
Verzija publikacijeObjavljena verzija rada (izdavačev PDF)
Naslov časopisaeBioMedicine
Brojčani podacivol. 94, 104692
p-ISSN2352-3964
DOIhttps://doi.org/10.1016/j.ebiom.2023.104692
URN:NBNurn:nbn:hr:105:015489
Datum objave publikacije2023-08
URL dokumentahttps://linkinghub.elsevier.com/retrieve/pii/S2352396423002578
Vrsta resursaTekst
Prava pristupaOtvoreni pristup
Uvjeti korištenjaIkona licence Imenovanje 4.0 međunarodna (CC BY 4.0)
Datum i vrijeme pohrane2024-09-25 11:19:53