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.

Cencelli, G., Pedini, G., Ricci, C., Rosina, E., Cecchetti, G., Gentile, A., et al. (2024). Early dysregulation of GSK3β impairs mitochondrial activity in Fragile X Syndrome. NEUROBIOLOGY OF DISEASE, 203, 1-13 [10.1016/j.nbd.2024.106726].

Early dysregulation of GSK3β impairs mitochondrial activity in Fragile X Syndrome

Cencelli, Giulia;Pedini, Giorgia;Ricci, Carlotta;Rosina, Eleonora;Cecchetti, Giorgia;Gentile, Antonietta;Pacini, Laura;Bagni, Claudia
2024-11-05

Abstract

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.
5-nov-2024
Pubblicato
Rilevanza internazionale
Articolo
Esperti anonimi
Settore BIO/13
Settore BIOS-10/A - Biologia cellulare e applicata
English
Autism
Coactivator (PGC) 1-alpha
GSK3β-inhibitor
Intellectual disabilities
Peroxisome Proliferator-Activated Receptor Gamma
Cencelli, G., Pedini, G., Ricci, C., Rosina, E., Cecchetti, G., Gentile, A., et al. (2024). Early dysregulation of GSK3β impairs mitochondrial activity in Fragile X Syndrome. NEUROBIOLOGY OF DISEASE, 203, 1-13 [10.1016/j.nbd.2024.106726].
Cencelli, G; Pedini, G; Ricci, C; Rosina, E; Cecchetti, G; Gentile, A; Aiello, G; Pacini, L; Garrone, B; Ombrato, R; Coletta, I; Prati, F; Milanese, C...espandi
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2108/395328
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