GSK-3 in neuronal plasticity and neurodegeneration: basic mechanisms and pre-clinical assessment (NEURO.GSK3)

Title of project or programme
GSK-3 in neuronal plasticity and neurodegeneration: basic mechanisms and pre-clinical assessment (NEURO.GSK3)
Principal Investigators of project/programme grant

Title	Forname	Surname	Institution	Country
Professor	Fred	van Leuven	KATHOLIEKE UNIVERSITEIT LEUVEN	Belgium

Address of institution of lead PI

Institution	KATHOLIEKE UNIVERSITEIT LEUVEN
Street Address
City
Postcode

Country
Belgium
Source of funding information
European Commission
Total sum awarded (Euro)
3573842
Start date of award
01-10-2008
Total duration of award in months
39
The project/programme is most relevant to

Alzheimer’s disease and other dementias

Keywords
Alzheimer,plasticity,spines,GSK3,tauopathy,kinase-inhibitors
Research abstract in English
Neuronal circuits in mammalian brain act predominantly via excitatory synapses on dendritic spines. Formation of new spines in adult brain constitutes the structural basis of neuronal plasticity. The underlying molecular mechanisms remain largely unknown but depend essentially on kinase-dependent signalling pathways. Final formation of synapses on spines depends on dynamic interactions of microtubuli and actin-filaments that are also controlled by kinases. Deterioration of these processes to different extents are thought to cause the cognitive decline in normal ageing as well in Alzheimer’s disease (AD) and familial fronto-temporal dementia (FTD).

Protein tau is a microtubule associated protein and GSK-3 kinases are proposed as the major tau-kinases in vivo. Their exact contributions remain to be functionally defined in vivo both in normal neuronal plasticity and in degeneration. We develop pre-clinical models for AD and FTD that have tauopathy in common as essential pathogenic component and will explore the GSK-3 kinases in vivo by manipulating their activity genetically, pharmacologically and biochemically. Inhibitors are wanted that are effective and specific and enter brain in vivo.
Lay summary

GSK-3 in neuronal plasticity and neurodegeneration: basic mechanisms and pre-clinical assessment (NEURO.GSK3)

Investments > €500k
Belgium
Alzheimer’s disease & other dementias
2011