Early dysregulation of GSK3β impairs mitochondrial activity in Fragile X Syndrome.

Autor: Cencelli G; Department of Biomedicine and Prevention, University of Rome Tor Vergata, 00133 Rome, Italy., Pedini G; Department of Biomedicine and Prevention, University of Rome Tor Vergata, 00133 Rome, Italy., Ricci C; Department of Biomedicine and Prevention, University of Rome Tor Vergata, 00133 Rome, Italy., Rosina E; Department of Biomedicine and Prevention, University of Rome Tor Vergata, 00133 Rome, Italy., Cecchetti G; Department of Biomedicine and Prevention, University of Rome Tor Vergata, 00133 Rome, Italy., Gentile A; Department of Biomedicine and Prevention, University of Rome Tor Vergata, 00133 Rome, Italy., Aiello G; Department of Fundamental Neurosciences, University of Lausanne, 1005 Lausanne, Switzerland., Pacini L; Department of Biomedicine and Prevention, University of Rome Tor Vergata, 00133 Rome, Italy; Faculty of Medicine, UniCamillus, Saint Camillus International University of Health and Medical Sciences, 00131 Rome, Italy., Garrone B; Angelini Pharma S.p.A., 00181 Rome, Italy., Ombrato R; Angelini Pharma S.p.A., 00181 Rome, Italy., Coletta I; Angelini Pharma S.p.A., 00181 Rome, Italy., Prati F; Angelini Pharma S.p.A., 00181 Rome, Italy., Milanese C; Angelini Pharma S.p.A., 00181 Rome, Italy., Bagni C; Department of Biomedicine and Prevention, University of Rome Tor Vergata, 00133 Rome, Italy; Department of Fundamental Neurosciences, University of Lausanne, 1005 Lausanne, Switzerland. Electronic address: claudia.bagni@unil.ch.
Jazyk: angličtina
Zdroj: Neurobiology of disease [Neurobiol Dis] 2024 Dec; Vol. 203, pp. 106726. Date of Electronic Publication: 2024 Nov 05.
DOI: 10.1016/j.nbd.2024.106726
Abstrakt: The finely tuned regulation of mitochondria activity is essential for proper brain development. Fragile X Syndrome (FXS), the leading cause of inherited intellectual disability, is a neurodevelopmental disorder in which mitochondrial dysfunction has been increasingly implicated. This study investigates the role of Glycogen Synthase Kinase 3β (GSK3β) in FXS. Several studies have reported the dysregulation of GSK3β in FXS, and its role in mitochondrial function is also well established. However, the link between disrupted GSK3β activity and mitochondrial dysfunction in FXS remains unexplored. Utilizing Fmr1 knockout (KO) mice and human cell lines from individuals with FXS, we uncovered a developmental window where dysregulated GSK3β activity disrupts mitochondrial function. Notably, a partial inhibition of GSK3β activity in FXS fibroblasts from young individuals rescues the observed mitochondrial defects, suggesting that targeting GSK3β in the early stages may offer therapeutic benefits for this condition.
Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:
(Copyright © 2024. Published by Elsevier Inc.)
Databáze: MEDLINE
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