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

Details

Ressource 1Download: 39510449.pdf (7679.34 [Ko])
State: Public
Version: Final published version
License: CC BY-NC-ND 4.0
Serval ID
serval:BIB_BF06FD998383
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Early dysregulation of GSK3β impairs mitochondrial activity in Fragile X Syndrome.
Journal
Neurobiology of disease
Author(s)
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., Bagni C.
ISSN
1095-953X (Electronic)
ISSN-L
0969-9961
Publication state
Published
Issued date
12/2024
Peer-reviewed
Oui
Volume
203
Pages
106726
Language
english
Notes
Publication types: Journal Article
Publication Status: ppublish
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.
Keywords
Fragile X Syndrome/metabolism, Fragile X Syndrome/genetics, Fragile X Syndrome/pathology, Glycogen Synthase Kinase 3 beta/metabolism, Animals, Mitochondria/metabolism, Humans, Mice, Knockout, Fragile X Mental Retardation Protein/genetics, Fragile X Mental Retardation Protein/metabolism, Mice, Fibroblasts/metabolism, Male, Mice, Inbred C57BL, Autism, Coactivator (PGC) 1-alpha, GSK3β-inhibitor, Intellectual disabilities, Peroxisome Proliferator-Activated Receptor Gamma
Pubmed
Web of science
Open Access
Yes
Create date
18/11/2024 12:07
Last modification date
09/01/2025 7:17
Usage data