Technologies
This technology is an optogenetic platform that enables precise control of phosphoinositide signaling to study and validate therapeutic targets for Alzheimer’s disease.
Phosphatidylinositol-4,5-bisphosphate PI(4,5)P2 is a signaling lipid that regulates essential synaptic functions and is depleted in Alzheimer’s disease. Determining whether restoring PI(4,5)P2 can protect neuronal function and serve as a therapeutic strategy requires precise control over when and where the lipid is produced. However, existing genetic and pharmacological approaches lack the spatial and temporal precision needed to selectively manipulate phosphoinositide signaling. Therefore, there is a need for technologies that enable rapid, reversible, and localized control of phosphoinositide signaling in living systems.
This technology is an optogenetic system that uses blue light to precisely control production of the signaling lipid PI(4,5)P2 in living cells and brain tissue. By recruiting phosphoinositide kinases to the cell membrane in response to light, the platform enables rapid, localized and reversible production of PI(4,5)P2 with high spatial and temporal precision. The system can be delivered using gene therapy vectors and activated in vivo to study phosphoinositide signaling and evaluate therapeutic strategies for Alzheimer’s disease and other neurological disorders.
The system has been validated in human cells and in a mouse model of Alzheimer’s disease, where light-induced PI(4,5)P2 production restored hippocampal learning and memory despite the presence of amyloid-β plaques.