000135955 001__ 135955
000135955 005__ 20240704095849.0
000135955 0247_ $$2doi$$a10.1016/j.redox.2024.103242
000135955 0248_ $$2sideral$$a139020
000135955 037__ $$aART-2024-139020
000135955 041__ $$aeng
000135955 100__ $$aCorreas, Ángela G.
000135955 245__ $$aGlucose 6 phosphate dehydrogenase overexpression rescues the loss of cognition in the double transgenic APP/PS1 mouse model of Alzheimer’s disease
000135955 260__ $$c2024
000135955 5060_ $$aAccess copy available to the general public$$fUnrestricted
000135955 5203_ $$aMice models of Alzheimer's disease (APP/PS1) typically experience cognitive decline with age. G6PD overexpressing mice (G6PD-Tg) exhibit better protection from age-associated functional decline including improvements in metabolic and muscle functions as well as reduced frailty compared to their wild-type counterparts. Importantly G6PD-Tg mice show diminished accumulation of DNA oxidation in the brain at different ages in both males and females. To further explore the potential benefits of modulating the G6PD activity in neurodegenerative diseases, triple transgenic mice (3xTg G6PD) were generated, overexpressing APP, PSEN1, and G6PD genes. The cognitive decline characteristic of APP/PS1 mice was prevented in 3xTg G6PD mice, despite similar amyloid-β (Aβ) levels in the hippocampus. This challenges the dominant hypothesis in Alzheimer's disease (AD) etiology and the majority of therapeutic efforts in the field, based on the notion that Aβ is pivotal in cognitive preservation. Notably, the antioxidant properties of G6PD led to a decrease in oxidative stress parameters, such as improved GSH/GSSG and GSH/CysSSG ratios, without major changes in oxidative damage markers. Additionally, metabolic changes in 3xTg G6PD mice increased brain energy status, countering the hypometabolism observed in Alzheimer's models. Remarkably, a higher respiratory exchange ratio suggested increased carbohydrate utilization. The relative failures of Aβ-targeted clinical trials have raised significant skepticism on the amyloid cascade hypothesis and whether the development of Alzheimer's drugs has followed the correct path. Our findings highlight the significance of targeting glucose-metabolizing enzymes rather than solely focusing on Aβ in Alzheimer's research, advocating for a deeper exploration of glucose metabolism's role in cognitive preservation.
000135955 536__ $$9info:eu-repo/grantAgreement/ES/AEI/PID2022-142470OB-I00$$9info:eu-repo/grantAgreement/ES/AEI/RED2022-134800-T$$9info:eu-repo/grantAgreement/EC/H2020/825546/EU/Scaling-up of and evidence-based intervention programme in older people with Diabetes and Frailty in LatinAmerica/DIABFRAIL-LATAM$$9This project has received funding from the European Union’s Horizon 2020 research and innovation program under grant agreement No H2020 825546-DIABFRAIL-LATAM$$9info:eu-repo/grantAgreement/ES/MICINN/ISCIII CB16-10-00435
000135955 540__ $$9info:eu-repo/semantics/openAccess$$aby-nc-nd$$uhttp://creativecommons.org/licenses/by-nc-nd/3.0/es/
000135955 655_4 $$ainfo:eu-repo/semantics/article$$vinfo:eu-repo/semantics/publishedVersion
000135955 700__ $$aOlaso-Gonzalez, Gloria
000135955 700__ $$aRoca, Marta
000135955 700__ $$0(orcid)0000-0001-5990-1266$$aBlanco-Gandía, Mari Carmen$$uUniversidad de Zaragoza
000135955 700__ $$aNascimento, Carla
000135955 700__ $$aLahoz, Agustín
000135955 700__ $$aRodríguez-Arias, Marta
000135955 700__ $$aMiñarro, José
000135955 700__ $$aGómez-Cabrera, Mari Carmen
000135955 700__ $$aViña, José
000135955 7102_ $$14009$$2735$$aUniversidad de Zaragoza$$bDpto. Psicología y Sociología$$cÁrea Psicolog.Evolut.Educac
000135955 773__ $$g75 (2024), 103242 [12 pp.]$$pRedox biol.$$tRedox Biology$$x2213-2317
000135955 8564_ $$s5081921$$uhttps://zaguan.unizar.es/record/135955/files/texto_completo.pdf$$yVersión publicada
000135955 8564_ $$s2276122$$uhttps://zaguan.unizar.es/record/135955/files/texto_completo.jpg?subformat=icon$$xicon$$yVersión publicada
000135955 909CO $$ooai:zaguan.unizar.es:135955$$particulos$$pdriver
000135955 951__ $$a2024-07-04-07:59:03
000135955 980__ $$aARTICLE