GSK-3 in neuronal plasticity and neurodegeneration: basic mechanisms and pre-clinical assessment (NEURO.GSK3)
|Professor||Fred||van Leuven||KATHOLIEKE UNIVERSITEIT LEUVEN||Belgium|
|Institution||KATHOLIEKE UNIVERSITEIT LEUVEN|
- Alzheimer’s disease and other dementias
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.