GSK-3β at the Intersection of Neuronal Plasticity and Neurodegeneration
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TLDR
An overview of how GSK-3β is regulated in physiological synaptic plasticity and how aberrant G SK-3 β activity contributes to the development of dysfunctional synaptic Plasticity in neuropsychiatric and neurodegenerative disorders is provided.Abstract:
In neurons, Glycogen Synthase Kinase-3β (GSK-3β) has been shown to regulate various critical processes underlying structural and functional synaptic plasticity. Mouse models with neuron-selective expression or deletion of GSK-3β present behavioral and cognitive abnormalities, positioning this protein kinase as a key signaling molecule in normal brain functioning. Furthermore, mouse models with defective GSK-3β activity display distinct structural and behavioral abnormalities, which model some aspects of different neurological and neuropsychiatric disorders. Equalizing GSK-3β activity in these mouse models by genetic or pharmacological interventions is able to rescue some of these abnormalities. Thus, GSK-3β is a relevant therapeutic target for the treatment of many brain disorders. Here, we provide an overview of how GSK-3β is regulated in physiological synaptic plasticity and how aberrant GSK-3β activity contributes to the development of dysfunctional synaptic plasticity in neuropsychiatric and neurodegenerative disorders.read more
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GSK-3: tricks of the trade for a multi-tasking kinase.
TL;DR: Since increased GSK-3 activity may be linked to pathology in diseases such as Alzheimer's disease and non-insulin-dependent diabetes mellitus, several new G SKS-3 inhibitors, such as the aloisines, the paullones and the maleimides, have been developed and hold promise as therapeutic agents.
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