The physiological and pathological contribution of GSK3 isozymes in normal mice and transgenic Alzheimer mice models.

Alzheimers disease (AD) is the most common form of senile dementia, whereby neurodegeneration is preceded by amyloid and tau pathologie. Although this combination is diagnostic for AD, neither their relation nor their relative pathological role is exactly known. Therefore we propose an important role for Glycogen Synthase Kinase 3. GSK3 consists of two strongly homologous isozymes (GSK3α, GSK3β) which are important in normal and pathological neurobiology. However, there is not much known about the normal physiological functions in the adult brain of both GSK3 isozymes.
 
This project therefore addresses in the first place the experimental definition of the fundamental, neuron-specific fysiologie of both GSK3 isozymes, by phenotypical characterization of neuron-specific GSK3α or GSK3β knock-out mice.
 
This project addresses further the pathological role of both isozymes in pre-clinical transgenic mice-models. The contribution of both GSK3 isozymes to pathology and neurodegeneration will be investigated by crossing the neuron-specific GSK3 knock-outs with mice which express either amyloid pathology, tau pathology or both.

Keywords:Alzheimer's Dementia (AD), Glycogen Synthase Kinase 3 (GSK3), Tau, APP, Fysiology, Pathology, Transgenic and pre-clinical mice models, neurodegeneration, cognition

Disciplines:Animal biology, General biology, Genetics, Systems biology, Molecular and cell biology, Morphological sciences, Biochemistry and metabolism, Medical biochemistry and metabolism

Project type:PhD project