The Role of Homer in the Pathogenesis of Alzheimer's Disease
Homer proteins are scaffolding, or organising proteins at the synapse involved in transducing the effects of intracellular calcium within the neuron. Homer is important in the adult brain for learning and memory and can couple and facilitate signaling molecules at the synapse, thereby enhancing communication between neurons. In a transgenic mouse model for Alzheimer's disease there is aberrant Homer expression that coincides with an onset of cognition decline. Homer reportedly interacts with proteins crucial to the Alzheimer's disease process, the amyloid precursor protein (APP) and the β-secretase, also known as BACE1 (the enzyme that cleaves APP to form A&beta).
The aim of this project is to examine expression levels of specific Homer isoforms in Alzheimer's disease, using transgenic models and sections from human brain.
We are currently
- Examining whether changes in Homer expression correlates with other pathogenic changes in a transgenic mouse model of Alzheimer's disease
- Determining whether Homer proteins bind directly APP and A&beta protein to modify Ca++ signaling in central neurons
- Examining the effect of A&beta protein on the expression of Homer in cell culture models of A&beta neurotoxicity
- Professor David Small (Professorial Fellow)
- Associate Professor Lisa Foa (Lecturer)
- Dr Rob Gasperini (Research Fellow)