Bauchwitz, Dr. Robert P. (2007) Elevated glycogen synthase kinase 3 activity in Fragile X mice: key metabolic regulator with evidence for treatment potential. [Preprint]
This is the latest version of this eprint.
Full text available as:
![]() |
PDF (Min_et_al_2007_FX-GSK3_submitted012908.pdf)
- Submitted Version
Restricted to Registered users only 547Kb | |
![]() |
PDF (Min_et_al_2007_FX-GSK3_Supplemental_Info_submitted012908.pdf)
- Submitted Version
Restricted to Registered users only 125Kb | |
![]()
|
PDF (Min_et.al._FX-GSK3_2008_NP_online.pdf)
- Published Version
551Kb | |
![]()
|
PDF (Min_et.al._FX-GSK3_Supplemental_Info_NP_online.pdf)
- Published Version
423Kb |
Abstract
Significant advances have been made in understanding the underlying defects of and developing potential treatments for Fragile X Syndrome (FXS), the most common heritable mental retardation. It has been shown that neuronal mGluR5-mediated signaling is affected in FX animal models, with consequent alterations in activity-dependent protein translation and synaptic spine functionality. We demonstrate here that a central metabolic regulatory enzyme, glycogen synthase kinase 3 (GSK3) is present in a form indicating elevated activity in several regions of the FX mouse brain. Furthermore, we show that selective GSK3 inhibitors, as well as lithium, are able to revert mutant phenotypes of the FX mouse. Lithium, in particular, remained active with chronic dosing, although its effects were transient even when given from birth. The combination of mGluR5 antagonist and GSK3 inhibitors was not additive. Instead, it was discovered that mGluR5 signaling and GSK3 activation in the FX mouse are coordinately elevated, with inhibition of mGluR5 leading to inhibition of GSK3. These findings raise the possibility that GSK3 is a fundamental and central component of FXS pathology, with a substantial treatment potential.
Item Type: | Preprint |
---|---|
Keywords: | GSK3, Fragile X Syndrome, mental retardation, lithium, autism |
Subjects: | Neuroscience > Neuropharmacology |
ID Code: | 5925 |
Deposited By: | Bauchwitz, Robert |
Deposited On: | 10 Feb 2008 03:27 |
Last Modified: | 11 Mar 2011 08:57 |
Available Versions of this Item
-
Elevated glycogen synthase kinase 3 activity in Fragile X mice: key metabolic regulator with evidence for treatment potential. (deposited 01 Jan 2008 15:06)
- Elevated glycogen synthase kinase 3 activity in Fragile X mice: key metabolic regulator with evidence for treatment potential. (deposited 10 Feb 2008 03:27) [Currently Displayed]
References in Article
Select the SEEK icon to attempt to find the referenced article. If it does not appear to be in cogprints you will be forwarded to the paracite service. Poorly formated references will probably not work.
Metadata
- ASCII Citation
- Atom
- BibTeX
- Dublin Core
- EP3 XML
- EPrints Application Profile (experimental)
- EndNote
- HTML Citation
- ID Plus Text Citation
- JSON
- METS
- MODS
- MPEG-21 DIDL
- OpenURL ContextObject
- OpenURL ContextObject in Span
- RDF+N-Triples
- RDF+N3
- RDF+XML
- Refer
- Reference Manager
- Search Data Dump
- Simple Metadata
- YAML
Repository Staff Only: item control page